U.S. Route 278

U.S. Route 278 is a parallel route of U.S. Route 78. It currently runs for 1,074 miles (1,728 km) from Hilton Head Island, South Carolina to Wickes, Arkansas at U.S. Route 71/U.S. Route 59. It is longer than its parent highway, US Hwy-78. US Hwy-278 passes through the states of South Carolina, Georgia, Alabama, Mississippi, and Arkansas. This highway passes through the cities and towns of Augusta, Covington, Atlanta, Powder Springs, Georgia; Hiram, Georgia; Dallas, Georgia; Rockmart, Georgia; Cedartown, Georgia; Gadsden, Cullman, Alabama; Tupelo, Oxford, Greenville, Mississippi; Monticello, and Hope, Arkansas.

It also passes through the Savannah River Site, of the Department of Energy in South Carolina, and crosses the Tennessee-Tombigbee Waterway in eastern Mississippi.

U.S. 278 passes through the places where many colleges, universities, and technical institutes are located, including the Georgia Institute of Technology, Georgia State University, and many others in Atlanta, Georgia; the Augusta State University; the University of Mississippi, and the University of Arkansas at Monticello.