diff --git a/crates/uv/src/commands/project/add.rs b/crates/uv/src/commands/project/add.rs
index 394592b17ba1..21abff893558 100644
--- a/crates/uv/src/commands/project/add.rs
+++ b/crates/uv/src/commands/project/add.rs
@@ -992,9 +992,27 @@ fn resolve_requirement(
     Ok((processed_requirement, source))
 }
 
+/// A Python [`Interpreter`] or [`PythonEnvironment`] for a project.
+#[derive(Debug, Clone)]
+#[allow(clippy::large_enum_variant)]
+pub(super) enum PythonTarget {
+    Interpreter(Interpreter),
+    Environment(PythonEnvironment),
+}
+
+impl PythonTarget {
+    /// Return the [`Interpreter`] for the project.
+    fn interpreter(&self) -> &Interpreter {
+        match self {
+            Self::Interpreter(interpreter) => interpreter,
+            Self::Environment(venv) => venv.interpreter(),
+        }
+    }
+}
+
 /// Represents the destination where dependencies are added, either to a project or a script.
 #[derive(Debug, Clone)]
-enum AddTarget {
+pub(super) enum AddTarget {
     /// A PEP 723 script, with inline metadata.
     Script(Pep723Script, Box<Interpreter>),
 
@@ -1013,7 +1031,7 @@ impl<'lock> From<&'lock AddTarget> for LockTarget<'lock> {
 
 impl AddTarget {
     /// Returns the [`Interpreter`] for the target.
-    fn interpreter(&self) -> &Interpreter {
+    pub(super) fn interpreter(&self) -> &Interpreter {
         match self {
             Self::Script(_, interpreter) => interpreter,
             Self::Project(_, venv) => venv.interpreter(),
@@ -1133,24 +1151,6 @@ impl AddTargetSnapshot {
     }
 }
 
-/// A Python [`Interpreter`] or [`PythonEnvironment`] for a project.
-#[derive(Debug, Clone)]
-#[allow(clippy::large_enum_variant)]
-enum PythonTarget {
-    Interpreter(Interpreter),
-    Environment(PythonEnvironment),
-}
-
-impl PythonTarget {
-    /// Return the [`Interpreter`] for the project.
-    fn interpreter(&self) -> &Interpreter {
-        match self {
-            Self::Interpreter(interpreter) => interpreter,
-            Self::Environment(venv) => venv.interpreter(),
-        }
-    }
-}
-
 #[derive(Debug, Clone)]
 struct DependencyEdit {
     dependency_type: DependencyType,
diff --git a/crates/uv/src/commands/project/remove.rs b/crates/uv/src/commands/project/remove.rs
index 415115aa358a..d68a0f789004 100644
--- a/crates/uv/src/commands/project/remove.rs
+++ b/crates/uv/src/commands/project/remove.rs
@@ -1,9 +1,10 @@
-use std::fmt::Write;
-use std::path::Path;
-
 use anyhow::{Context, Result};
 use owo_colors::OwoColorize;
-
+use std::fmt::Write;
+use std::io;
+use std::path::Path;
+use std::str::FromStr;
+use tracing::debug;
 use uv_cache::Cache;
 use uv_client::Connectivity;
 use uv_configuration::{
@@ -15,7 +16,7 @@ use uv_fs::Simplified;
 use uv_normalize::DEV_DEPENDENCIES;
 use uv_pep508::PackageName;
 use uv_python::{PythonDownloads, PythonPreference, PythonRequest};
-use uv_scripts::Pep723Script;
+use uv_scripts::{Pep723Item, Pep723Metadata, Pep723Script};
 use uv_settings::PythonInstallMirrors;
 use uv_warnings::warn_user_once;
 use uv_workspace::pyproject::DependencyType;
@@ -24,9 +25,13 @@ use uv_workspace::{DiscoveryOptions, VirtualProject, Workspace};
 
 use crate::commands::pip::loggers::{DefaultInstallLogger, DefaultResolveLogger};
 use crate::commands::pip::operations::Modifications;
+use crate::commands::project::add::{AddTarget, PythonTarget};
 use crate::commands::project::install_target::InstallTarget;
 use crate::commands::project::lock::LockMode;
-use crate::commands::project::{default_dependency_groups, ProjectError};
+use crate::commands::project::lock_target::LockTarget;
+use crate::commands::project::{
+    default_dependency_groups, ProjectError, ProjectInterpreter, ScriptInterpreter,
+};
 use crate::commands::{diagnostics, project, ExitStatus};
 use crate::printer::Printer;
 use crate::settings::ResolverInstallerSettings;
@@ -79,7 +84,7 @@ pub(crate) async fn remove(
                 "`--no-sync` is a no-op for Python scripts with inline metadata, which always run in isolation"
             );
         }
-        Target::Script(script)
+        RemoveTarget::Script(script)
     } else {
         // Find the project in the workspace.
         let project = if let Some(package) = package {
@@ -93,14 +98,14 @@ pub(crate) async fn remove(
             VirtualProject::discover(project_dir, &DiscoveryOptions::default()).await?
         };
 
-        Target::Project(project)
+        RemoveTarget::Project(project)
     };
 
     let mut toml = match &target {
-        Target::Script(script) => {
+        RemoveTarget::Script(script) => {
             PyProjectTomlMut::from_toml(&script.metadata.raw, DependencyTarget::Script)
         }
-        Target::Project(project) => PyProjectTomlMut::from_toml(
+        RemoveTarget::Project(project) => PyProjectTomlMut::from_toml(
             project.pyproject_toml().raw.as_ref(),
             DependencyTarget::PyProjectToml,
         ),
@@ -161,27 +166,20 @@ pub(crate) async fn remove(
         }
     }
 
-    // Save the modified dependencies.
-    match &target {
-        Target::Script(script) => {
-            script.write(&toml.to_string())?;
-        }
-        Target::Project(project) => {
-            let pyproject_path = project.root().join("pyproject.toml");
-            fs_err::write(pyproject_path, toml.to_string())?;
-        }
-    };
+    let content = toml.to_string();
 
-    // If `--frozen`, exit early. There's no reason to lock and sync, and we don't need a `uv.lock`
+    // Save the modified `pyproject.toml` or script.
+    target.write(&content)?;
+
+    // If `--frozen`, exit early. There's no reason to lock and sync, since we don't need a `uv.lock`
     // to exist at all.
     if frozen {
         return Ok(ExitStatus::Success);
     }
 
-    let project = match target {
-        Target::Project(project) => project,
-        // If `--script`, exit early. There's no reason to lock and sync.
-        Target::Script(script) => {
+    // If we're modifying a script, and lockfile doesn't exist, don't create it.
+    if let RemoveTarget::Script(ref script) = target {
+        if !LockTarget::from(script).lock_path().is_file() {
             writeln!(
                 printer.stderr(),
                 "Updated `{}`",
@@ -189,31 +187,80 @@ pub(crate) async fn remove(
             )?;
             return Ok(ExitStatus::Success);
         }
-    };
+    }
 
-    // Discover or create the virtual environment.
-    let venv = project::get_or_init_environment(
-        project.workspace(),
-        python.as_deref().map(PythonRequest::parse),
-        &install_mirrors,
-        python_preference,
-        python_downloads,
-        connectivity,
-        native_tls,
-        allow_insecure_host,
-        no_config,
-        cache,
-        printer,
-    )
-    .await?;
+    // Update the `pypackage.toml` in-memory.
+    let target = target.update(&content)?;
+
+    // Convert to an `AddTarget` by attaching the appropriate interpreter or environment.
+    let target = match target {
+        RemoveTarget::Project(project) => {
+            if no_sync {
+                // Discover the interpreter.
+                let interpreter = ProjectInterpreter::discover(
+                    project.workspace(),
+                    project_dir,
+                    python.as_deref().map(PythonRequest::parse),
+                    python_preference,
+                    python_downloads,
+                    connectivity,
+                    native_tls,
+                    allow_insecure_host,
+                    &install_mirrors,
+                    no_config,
+                    cache,
+                    printer,
+                )
+                .await?
+                .into_interpreter();
+
+                AddTarget::Project(project, Box::new(PythonTarget::Interpreter(interpreter)))
+            } else {
+                // Discover or create the virtual environment.
+                let venv = project::get_or_init_environment(
+                    project.workspace(),
+                    python.as_deref().map(PythonRequest::parse),
+                    &install_mirrors,
+                    python_preference,
+                    python_downloads,
+                    connectivity,
+                    native_tls,
+                    allow_insecure_host,
+                    no_config,
+                    cache,
+                    printer,
+                )
+                .await?;
+
+                AddTarget::Project(project, Box::new(PythonTarget::Environment(venv)))
+            }
+        }
+        RemoveTarget::Script(script) => {
+            let interpreter = ScriptInterpreter::discover(
+                &Pep723Item::Script(script.clone()),
+                python.as_deref().map(PythonRequest::parse),
+                python_preference,
+                python_downloads,
+                connectivity,
+                native_tls,
+                allow_insecure_host,
+                &install_mirrors,
+                no_config,
+                cache,
+                printer,
+            )
+            .await?
+            .into_interpreter();
+
+            AddTarget::Script(script, Box::new(interpreter))
+        }
+    };
 
     // Determine the lock mode.
-    let mode = if frozen {
-        LockMode::Frozen
-    } else if locked {
-        LockMode::Locked(venv.interpreter())
+    let mode = if locked {
+        LockMode::Locked(target.interpreter())
     } else {
-        LockMode::Write(venv.interpreter())
+        LockMode::Write(target.interpreter())
     };
 
     // Initialize any shared state.
@@ -222,7 +269,7 @@ pub(crate) async fn remove(
     // Lock and sync the environment, if necessary.
     let lock = match project::lock::do_safe_lock(
         mode,
-        project.workspace().into(),
+        (&target).into(),
         settings.as_ref().into(),
         LowerBound::Allow,
         &state,
@@ -246,9 +293,15 @@ pub(crate) async fn remove(
         Err(err) => return Err(err.into()),
     };
 
-    if no_sync {
+    let AddTarget::Project(project, environment) = target else {
+        // If we're not adding to a project, exit early.
         return Ok(ExitStatus::Success);
-    }
+    };
+
+    let PythonTarget::Environment(venv) = &*environment else {
+        // If we're not syncing, exit early.
+        return Ok(ExitStatus::Success);
+    };
 
     // Perform a full sync, because we don't know what exactly is affected by the removal.
     // TODO(ibraheem): Should we accept CLI overrides for this? Should we even sync here?
@@ -273,7 +326,7 @@ pub(crate) async fn remove(
 
     match project::sync::do_sync(
         target,
-        &venv,
+        venv,
         &extras,
         &DevGroupsManifest::from_defaults(defaults),
         EditableMode::Editable,
@@ -306,13 +359,62 @@ pub(crate) async fn remove(
 
 /// Represents the destination where dependencies are added, either to a project or a script.
 #[derive(Debug)]
-enum Target {
+enum RemoveTarget {
     /// A PEP 723 script, with inline metadata.
     Project(VirtualProject),
     /// A project with a `pyproject.toml`.
     Script(Pep723Script),
 }
 
+impl RemoveTarget {
+    /// Write the updated content to the target.
+    ///
+    /// Returns `true` if the content was modified.
+    fn write(&self, content: &str) -> Result<bool, io::Error> {
+        match self {
+            Self::Script(script) => {
+                if content == script.metadata.raw {
+                    debug!("No changes to dependencies; skipping update");
+                    Ok(false)
+                } else {
+                    script.write(content)?;
+                    Ok(true)
+                }
+            }
+            Self::Project(project) => {
+                if content == project.pyproject_toml().raw {
+                    debug!("No changes to dependencies; skipping update");
+                    Ok(false)
+                } else {
+                    let pyproject_path = project.root().join("pyproject.toml");
+                    fs_err::write(pyproject_path, content)?;
+                    Ok(true)
+                }
+            }
+        }
+    }
+
+    /// Update the target in-memory to incorporate the new content.
+    #[allow(clippy::result_large_err)]
+    fn update(self, content: &str) -> Result<Self, ProjectError> {
+        match self {
+            Self::Script(mut script) => {
+                script.metadata = Pep723Metadata::from_str(content)
+                    .map_err(ProjectError::Pep723ScriptTomlParse)?;
+                Ok(Self::Script(script))
+            }
+            Self::Project(project) => {
+                let project = project
+                    .with_pyproject_toml(
+                        toml::from_str(content).map_err(ProjectError::PyprojectTomlParse)?,
+                    )
+                    .ok_or(ProjectError::PyprojectTomlUpdate)?;
+                Ok(Self::Project(project))
+            }
+        }
+    }
+}
+
 /// Show a hint if a dependency with the given name is present as any dependency type.
 ///
 /// This is useful when a dependency of the user-specified type was not found, but it may be present
diff --git a/crates/uv/tests/it/edit.rs b/crates/uv/tests/it/edit.rs
index 82d8f39827e2..c2fe4a33c4a9 100644
--- a/crates/uv/tests/it/edit.rs
+++ b/crates/uv/tests/it/edit.rs
@@ -5334,9 +5334,9 @@ fn remove_repeated() -> Result<()> {
     Ok(())
 }
 
-/// Add to a PEP 732 script with a lockfile.
+/// Add to (and remove from) a PEP 732 script with a lockfile.
 #[test]
-fn add_script_lock() -> Result<()> {
+fn add_remove_script_lock() -> Result<()> {
     let context = TestContext::new("3.12");
 
     let script = context.temp_dir.child("script.py");
@@ -5718,10 +5718,191 @@ fn add_script_lock() -> Result<()> {
         );
     });
 
+    // Removing from a locked script should update the lockfile.
+    uv_snapshot!(context.filters(), context.remove().arg("anyio").arg("--script").arg("script.py"), @r###"
+    success: true
+    exit_code: 0
+    ----- stdout -----
+
+    ----- stderr -----
+    Resolved 9 packages in [TIME]
+    "###);
+
+    let script_content = context.read("script.py");
+
+    insta::with_settings!({
+        filters => context.filters(),
+    }, {
+        assert_snapshot!(
+            script_content, @r###"
+        # /// script
+        # requires-python = ">=3.11"
+        # dependencies = [
+        #   "requests<3",
+        #   "rich",
+        # ]
+        # ///
+
+        import requests
+        from rich.pretty import pprint
+
+        resp = requests.get("https://peps.python.org/api/peps.json")
+        data = resp.json()
+        pprint([(k, v["title"]) for k, v in data.items()][:10])
+        "###
+        );
+    });
+
+    let lock = context.read("script.py.lock");
+
+    insta::with_settings!({
+        filters => context.filters(),
+    }, {
+        assert_snapshot!(
+            lock, @r###"
+        version = 1
+        requires-python = ">=3.11"
+
+        [options]
+        exclude-newer = "2024-03-25T00:00:00Z"
+
+        [manifest]
+        requirements = [
+            { name = "requests", specifier = "<3" },
+            { name = "rich" },
+        ]
+
+        [[package]]
+        name = "certifi"
+        version = "2024.2.2"
+        source = { registry = "https://pypi.org/simple" }
+        sdist = { url = "https://files.pythonhosted.org/packages/71/da/e94e26401b62acd6d91df2b52954aceb7f561743aa5ccc32152886c76c96/certifi-2024.2.2.tar.gz", hash = "sha256:0569859f95fc761b18b45ef421b1290a0f65f147e92a1e5eb3e635f9a5e4e66f", size = 164886 }
+        wheels = [
+            { url = "https://files.pythonhosted.org/packages/ba/06/a07f096c664aeb9f01624f858c3add0a4e913d6c96257acb4fce61e7de14/certifi-2024.2.2-py3-none-any.whl", hash = "sha256:dc383c07b76109f368f6106eee2b593b04a011ea4d55f652c6ca24a754d1cdd1", size = 163774 },
+        ]
+
+        [[package]]
+        name = "charset-normalizer"
+        version = "3.3.2"
+        source = { registry = "https://pypi.org/simple" }
+        sdist = { url = "https://files.pythonhosted.org/packages/63/09/c1bc53dab74b1816a00d8d030de5bf98f724c52c1635e07681d312f20be8/charset-normalizer-3.3.2.tar.gz", hash = "sha256:f30c3cb33b24454a82faecaf01b19c18562b1e89558fb6c56de4d9118a032fd5", size = 104809 }
+        wheels = [
+            { url = "https://files.pythonhosted.org/packages/68/77/02839016f6fbbf808e8b38601df6e0e66c17bbab76dff4613f7511413597/charset_normalizer-3.3.2-cp311-cp311-macosx_10_9_universal2.whl", hash = "sha256:802fe99cca7457642125a8a88a084cef28ff0cf9407060f7b93dca5aa25480db", size = 191647 },
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+        version = "13.7.1"
+        source = { registry = "https://pypi.org/simple" }
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+        ]
+
+        [[package]]
+        name = "urllib3"
+        version = "2.2.1"
+        source = { registry = "https://pypi.org/simple" }
+        sdist = { url = "https://files.pythonhosted.org/packages/7a/50/7fd50a27caa0652cd4caf224aa87741ea41d3265ad13f010886167cfcc79/urllib3-2.2.1.tar.gz", hash = "sha256:d0570876c61ab9e520d776c38acbbb5b05a776d3f9ff98a5c8fd5162a444cf19", size = 291020 }
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+        ]
+        "###
+        );
+    });
+
     Ok(())
 }
 
-/// Remove from a PEP732 script,
+/// Remove from a PEP 723 script.
 #[test]
 fn remove_script() -> Result<()> {
     let context = TestContext::new("3.12");
@@ -5781,7 +5962,78 @@ fn remove_script() -> Result<()> {
     Ok(())
 }
 
-/// Remove last dependency PEP732 script
+/// Remove from a PEP 723 script.
+#[test]
+fn remove_script_lock() -> Result<()> {
+    let context = TestContext::new("3.12");
+
+    let script = context.temp_dir.child("script.py");
+    script.write_str(indoc! {r#"
+        # /// script
+        # requires-python = ">=3.11"
+        # dependencies = [
+        #   "requests<3",
+        #   "rich",
+        #   "anyio",
+        # ]
+        # ///
+
+        import requests
+        from rich.pretty import pprint
+
+        resp = requests.get("https://peps.python.org/api/peps.json")
+        data = resp.json()
+        pprint([(k, v["title"]) for k, v in data.items()][:10])
+    "#})?;
+
+    // Explicitly lock the script.
+    uv_snapshot!(context.filters(), context.lock().arg("--script").arg("script.py"), @r###"
+    success: true
+    exit_code: 0
+    ----- stdout -----
+
+    ----- stderr -----
+    Resolved 9 packages in [TIME]
+    "###);
+
+    uv_snapshot!(context.filters(), context.remove().arg("anyio").arg("--script").arg("script.py"), @r###"
+    success: true
+    exit_code: 0
+    ----- stdout -----
+
+    ----- stderr -----
+    Updated `script.py`
+    "###);
+
+    let script_content = context.read("script.py");
+
+    insta::with_settings!({
+        filters => context.filters(),
+    }, {
+        assert_snapshot!(
+            script_content, @r###"
+        # /// script
+        # requires-python = ">=3.11"
+        # dependencies = [
+        #   "requests<3",
+        #   "rich",
+        # ]
+        # ///
+
+        import requests
+        from rich.pretty import pprint
+
+        resp = requests.get("https://peps.python.org/api/peps.json")
+        data = resp.json()
+        pprint([(k, v["title"]) for k, v in data.items()][:10])
+        "###
+        );
+    });
+
+    Ok(())
+}
+
+/// Remove last dependency PEP 723 script
 #[test]
 fn remove_last_dep_script() -> Result<()> {
     let context = TestContext::new("3.12");
@@ -5836,7 +6088,7 @@ fn remove_last_dep_script() -> Result<()> {
     Ok(())
 }
 
-/// Add a Git requirement to PEP732 script.
+/// Add a Git requirement to PEP 723 script.
 #[test]
 #[cfg(feature = "git")]
 fn add_git_to_script() -> Result<()> {