U.S. Route 278 is a parallel route of US 78. It currently runs for 1,074 miles (1,728 km) from Hilton Head Island, South Carolina, to Wickes, Arkansas at US 71/US 59, passing through five states in the process. Landmarks along its route include the Department of Energy's Savannah River Site in South Carolina and the Tennessee-Tombigbee Waterway in eastern Mississippi. There are several universities located along the highway including Georgia State University, the University of Mississippi, and the University of Arkansas at Monticello.

U.S. Route 59 is a north–south United States highway. A latecomer to the U.S. numbered route system, US 59 is now a border-to-border route, part of the NAFTA Corridor Highway System. It parallels U.S. Route 75 for nearly its entire route, never much more than 100 miles (160 km) away, until it veers southwest in Houston, Texas. Its number is out of place since US 59 is either concurrent with or entirely west of U.S. Route 71. The highway's northern terminus is 9 mi (14 km) north of Lancaster, Minnesota, at the Lancaster–Tolstoi Border Crossing on the Canada–US border, where it continues as Manitoba Highway 59. Its southern terminus is at the Mexico–US border in Laredo, Texas, where it continues as Mexican Federal Highway 85D.