Entering Lake City, US 441 splits from US 41 onto State Road 25A south of the city. The routes remain parallel, and at the US 90 Lake City Truck Route, Route 441 is joined by State Road 47 which was signed as terminating at US 41. The first intersection within this new hidden route is at U.S. Route 90 (where the DeSoto Trail heads west) to the northern extents of Lake City. Past Lake City, SR 25 branches off to the northwest as County Road 25A, which also shares intersections with CR 250 to the east and Northeast Double Run Road to the northeast. US 441 has an interchange with Interstate 10 (Exit 303), then skirts the western edge of the Okefenokee Swamp and east bank of the Suwannee River as it enters Georgia.