U.S. Route 22 (US 22) is a major east–west route and one of the original United States Numbered Highways, founded in 1926. It runs from Cincinnati, Ohio, at US 27, US 42, US 127, and US 52 to Newark, New Jersey, at US 1/9 at the Newark Airport Interchange.
US 22 is named the William Penn Highway through most of Pennsylvania. In southwest Ohio, it overlaps with State Route 3 (SR 3) and is familiarly known as the 3-C Highway, "22 and 3", and Montgomery Road.