As the interstate was being built, the designation of US 21 was moved to the freeway before Ohio wholly decommissioned the now-superfluous U.S. route.

No segment of the route is included as a part of the National Highway System (NHS).

The NHS is a network of highways identified as being most important for the economy, mobility and defense of the nation.

The designation was applied to what was the former routing of US 21 between Marietta and Byesville, prior to the completion of I-77 through the area by 1969.

However, by 1971, it was introduced back into the system, and was given the designation of SR 821, based on its routing along the old path of US 21.