State Route 40 parallels the St. Marys River from U.S. Route 1/U.S. Route 23/U.S. Route 301 (State Route 4/State Route 15) in Folkston, Georgia east past U.S. Route 17 (State Route 25) and Interstate 95 (State Route 405) at Kingsland to end at Saint Marys. East of Kingsland it also parallels the St. Marys Railroad.