SR 121 begins in ruralCharlton County at the Florida state line near the southernmost point in the state. Here, the roadway continues as State Road 121. From the state line, it travels to the north, concurrent with SR 23. This segment of the route is called the Okefenokee Parkway. After passing through St. George, it has a concurrency with US 1/US 23/US 301/SR 4/SR 15 in Folkston. Shortly afterwards, US 301/SR 23 split from the other routes, while US 1/US 23/SR 4/SR 15/SR 121 stay concurrent until Race Point, where US 1/US 23/SR 4 continue to the northwest while SR 15/SR 121 branch off to the northeast. In Hoboken, the routes intersect with US 82/SR 520. In Blackshear is an intersection with US 84/SR 38. North of this intersection, SR 15 splits off to the northwest, while SR 121 heads to the northeast again. The road has a brief concurrency with SR 203 shortly afterwards. In Surrency, the road intersects US 341/SR 27. Later, SR 169, and then SR 144 form brief concurrencies with the road. A short time later, SR 23/SR 57 travel concurrent with the road. In Reidsville, the route intersects US 280/SR 30. In Cobbtown, SR 57 splits off. Just south of Metter is an interchange with Interstate 16 (I-16), specifically Exit 104. In Metter, SR 23 splits off. North of Metter, US 80/SR 26 intersect with the road. North of that junction, SR 121 begins a concurrency with US 25/SR 67. SR 23 joins the concurrency shortly afterward. In Millen, SR 23/SR 67 split off. SR 24 briefly joins the concurrency in Waynesboro. In Augusta, SR 121 travels concurrently with US 1/US 25/US 78/US 278/SR 10 along Gordon Highway and serves as a major road. At the South Carolina state line, SR 10/SR 121 end, while US 1/US 25/US 78/US 278 continue, concurrent with South Carolina Highway 121.