. US 22 is one of the original U.S. Routes, though in the 1925 plan it was to come to an end in Cleveland, Ohio, and it enters into Ohio on modern U.S. Route 422.
. In the finalized 1926 plan, it follows the recent course to U.S. Route 40, wherever it ended.
. During 1932, it had been extended to Cincinnati as it is currently; replace the Ohio State Route 10 and following preexisting State Route 3.