The highway is concurrent with various state highways in Georgia. It uses SR 4/SR 15 from the Florida state line to Homeland, SR 23 from Folkston to Glennville, SR 38 from Jesup to Ludowici, SR 57 from Ludowici to Glennville, SR 73 from Glennville to the South Carolina state line, and SR 73 Loop along the western edge of Sylvania. US 301 is concurrent with US 25 from Jesup to Statesboro.