My +1 is for the callback based approach. The brevity of the search loop for finding the innermost function is (in my opinion at least) non-obvious, relying on for loops not having their own scope as it does.

If a generator based API was adopted instead, I propose a convenience function (unwrap_all?) to help developers avoid writing code like:

    inner = None
    for inner in functools.unwrap(outer):
        pass
    if inner is None:
        inner = outer

Which combines a misunderstanding of the API with for loop scope shortcut.