diff --git a/Misc/NEWS.d/next/macOS/2024-09-11-08-00-19.gh-issue-123748.TOM9vt.rst b/Misc/NEWS.d/next/macOS/2024-09-11-08-00-19.gh-issue-123748.TOM9vt.rst
new file mode 100644
index 00000000000000..f965a32b0d0a43
--- /dev/null
+++ b/Misc/NEWS.d/next/macOS/2024-09-11-08-00-19.gh-issue-123748.TOM9vt.rst
@@ -0,0 +1 @@
+HACL* Blake2 SIMD256 has been disabled for universal2 builds on macOS.
diff --git a/configure b/configure
index 746c3b074d1fc3..2cb94105104149 100755
--- a/configure
+++ b/configure
@@ -30568,11 +30568,16 @@ printf "%s\n" "$ax_cv_check_cflags__Werror__mavx2" >&6; }
 if test "x$ax_cv_check_cflags__Werror__mavx2" = xyes
 then :
 
-  LIBHACL_SIMD256_FLAGS="-mavx2"
-  LIBHACL_SIMD256_OBJS="Modules/_hacl/Hacl_Hash_Blake2b_Simd256.o"
+  # macOS universal2 builds *support* the -mavx2 compiler flag because it's
+  # available on x86_64; but the HACL SIMD256 build then fails because the
+  # implementation requires symbols that aren't available on ARM64.
+  if test "$UNIVERSAL_ARCHS" != "universal2"; then
+    LIBHACL_SIMD256_FLAGS="-mavx2"
+    LIBHACL_SIMD256_OBJS="Modules/_hacl/Hacl_Hash_Blake2b_Simd256.o"
 
 printf "%s\n" "#define HACL_CAN_COMPILE_SIMD256 1" >>confdefs.h
 
+  fi
 
 else $as_nop
   :
diff --git a/configure.ac b/configure.ac
index 9284350695c526..2593a49d2f8093 100644
--- a/configure.ac
+++ b/configure.ac
@@ -7813,9 +7813,14 @@ AC_SUBST([LIBHACL_SIMD128_FLAGS])
 AC_SUBST([LIBHACL_SIMD128_OBJS])
 
 AX_CHECK_COMPILE_FLAG([-mavx2],[
-  [LIBHACL_SIMD256_FLAGS="-mavx2"]
-  [LIBHACL_SIMD256_OBJS="Modules/_hacl/Hacl_Hash_Blake2b_Simd256.o"]
-  AC_DEFINE([HACL_CAN_COMPILE_SIMD256], [1], [HACL* library can compile SIMD256 implementations])
+  # macOS universal2 builds *support* the -mavx2 compiler flag because it's
+  # available on x86_64; but the HACL SIMD256 build then fails because the
+  # implementation requires symbols that aren't available on ARM64.
+  if test "$UNIVERSAL_ARCHS" != "universal2"; then
+    [LIBHACL_SIMD256_FLAGS="-mavx2"]
+    [LIBHACL_SIMD256_OBJS="Modules/_hacl/Hacl_Hash_Blake2b_Simd256.o"]
+    AC_DEFINE([HACL_CAN_COMPILE_SIMD256], [1], [HACL* library can compile SIMD256 implementations])
+  fi
 ], [], [-Werror])
 
 AC_SUBST([LIBHACL_SIMD256_FLAGS])