State Route 22 is a south to north highway in Tennessee that is 156.5 miles (252.5 km) long, not counting its alternate and bypass sections. It begins in McNairy County and ends in Lake County, when it crosses into the Kentucky Bend, a detached portion of Fulton County, Kentucky.

The monument for the 1862 Battle of Island Number Ten in the American Civil War is located on Route 22, approximately three miles north of Tiptonville.

State Route 22 traverses the counties shown in the table below.