diff --git a/pkgs/tools/package-management/poetry/unwrapped.nix b/pkgs/tools/package-management/poetry/unwrapped.nix
index 59d7607600ff..550a8335e26c 100644
--- a/pkgs/tools/package-management/poetry/unwrapped.nix
+++ b/pkgs/tools/package-management/poetry/unwrapped.nix
@@ -151,6 +151,11 @@ buildPythonPackage rec {
     "poetry"
   ];
 
+  # Unset ambient PYTHONPATH in the wrapper, so Poetry only ever runs with its own,
+  # isolated set of dependencies. This works because the correct PYTHONPATH is set
+  # in the Python script, which runs after the wrapper.
+  makeWrapperArgs = ["--unset PYTHONPATH"];
+
   meta = with lib; {
     changelog = "https://github.com/python-poetry/poetry/blob/${src.rev}/CHANGELOG.md";
     homepage = "https://python-poetry.org/";