States traversed: Arkansas, Mississippi, Alabama, Georgia, and South Carolina
US Route 278 runs east-west across southern Arkansas, northern Mississippi, northern Alabama, and northern Georgia, before diving southeasterly in southern South Carolina. The western end is at US Routes 59 and 71 in Wickes, Arkansas, near the Oklahoma border. After crossing southern Arkansas, US Route 278 joins US Route 65 south to use US Route 82's bridge across the Mississippi River into the state of Mississippi, where it joins US Route 61 back north to its own alignment. US Route 278 crosses Mississippi and Alabama's northern sections before heading to Atlanta. East of Atlanta, US Route 278 hugs the Interstate 20 corridor to Augusta. At Augusta, Georgia, US Route 278 crosses into South Carolina and hugs that state's southwestern border. The eastern end of US Route 278 sits at US Route 17 in Ridgeland, South Carolina, near Interstate 95 and the southern tip of South Carolina.