diff --git a/crates/uv-resolver/src/lock/export/pylock_toml.rs b/crates/uv-resolver/src/lock/export/pylock_toml.rs
index ef3ad8615..642b9488a 100644
--- a/crates/uv-resolver/src/lock/export/pylock_toml.rs
+++ b/crates/uv-resolver/src/lock/export/pylock_toml.rs
@@ -186,7 +186,7 @@ pub struct PylockToml {
     lock_version: Version,
     created_by: String,
     #[serde(skip_serializing_if = "Option::is_none")]
-    requires_python: Option<RequiresPython>,
+    pub requires_python: Option<RequiresPython>,
     #[serde(skip_serializing_if = "Vec::is_empty", default)]
     pub extras: Vec<ExtraName>,
     #[serde(skip_serializing_if = "Vec::is_empty", default)]
diff --git a/crates/uv/src/commands/pip/install.rs b/crates/uv/src/commands/pip/install.rs
index 72c532d7b..cb1229d72 100644
--- a/crates/uv/src/commands/pip/install.rs
+++ b/crates/uv/src/commands/pip/install.rs
@@ -444,6 +444,17 @@ pub(crate) async fn pip_install(
             format!("Not a valid `pylock.toml` file: {}", pylock.user_display())
         })?;
 
+        // Verify that the Python version is compatible with the lock file.
+        if let Some(requires_python) = lock.requires_python.as_ref() {
+            if !requires_python.contains(interpreter.python_version()) {
+                return Err(anyhow::anyhow!(
+                    "The requested interpreter resolved to Python {}, which is incompatible with the `pylock.toml`'s Python requirement: `{}`",
+                    interpreter.python_version(),
+                    requires_python,
+                ));
+            }
+        }
+
         // Convert the extras and groups specifications into a concrete form.
         let extras = extras.with_defaults(DefaultExtras::default());
         let extras = extras
diff --git a/crates/uv/src/commands/pip/sync.rs b/crates/uv/src/commands/pip/sync.rs
index 2f46ef502..2fe5fbe87 100644
--- a/crates/uv/src/commands/pip/sync.rs
+++ b/crates/uv/src/commands/pip/sync.rs
@@ -382,6 +382,17 @@ pub(crate) async fn pip_sync(
             format!("Not a valid `pylock.toml` file: {}", pylock.user_display())
         })?;
 
+        // Verify that the Python version is compatible with the lock file.
+        if let Some(requires_python) = lock.requires_python.as_ref() {
+            if !requires_python.contains(interpreter.python_version()) {
+                return Err(anyhow::anyhow!(
+                    "The requested interpreter resolved to Python {}, which is incompatible with the `pylock.toml`'s Python requirement: `{}`",
+                    interpreter.python_version(),
+                    requires_python,
+                ));
+            }
+        }
+
         // Convert the extras and groups specifications into a concrete form.
         let extras = extras.with_defaults(DefaultExtras::default());
         let extras = extras
diff --git a/crates/uv/tests/it/pip_install.rs b/crates/uv/tests/it/pip_install.rs
index de62c4222..936f77aff 100644
--- a/crates/uv/tests/it/pip_install.rs
+++ b/crates/uv/tests/it/pip_install.rs
@@ -11590,6 +11590,51 @@ requires_python = "==3.13.*"
     Ok(())
 }
 
+#[test]
+fn pep_751_requires_python() -> Result<()> {
+    let context = TestContext::new_with_versions(&["3.12", "3.13"]);
+
+    let pyproject_toml = context.temp_dir.child("pyproject.toml");
+    pyproject_toml.write_str(
+        r#"
+        [project]
+        name = "project"
+        version = "0.1.0"
+        requires-python = ">=3.13"
+        dependencies = ["iniconfig"]
+        "#,
+    )?;
+
+    context
+        .export()
+        .arg("-o")
+        .arg("pylock.toml")
+        .assert()
+        .success();
+
+    context
+        .venv()
+        .arg("--python")
+        .arg("3.12")
+        .assert()
+        .success();
+
+    uv_snapshot!(context.filters(), context.pip_install()
+        .arg("--preview")
+        .arg("-r")
+        .arg("pylock.toml"), @r"
+    success: false
+    exit_code: 2
+    ----- stdout -----
+
+    ----- stderr -----
+    error: The requested interpreter resolved to Python 3.12.[X], which is incompatible with the `pylock.toml`'s Python requirement: `>=3.13`
+    "
+    );
+
+    Ok(())
+}
+
 /// Test that uv doesn't hang if an index returns a distribution for the wrong package.
 #[tokio::test]
 async fn bogus_redirect() -> Result<()> {