US 341 begins at an intersection with US 17 and SR 25 (Glynn Avenue) in the southeast corner of the city of Brunswick, a short distance north of the Sidney Lanier Bridge. US 341 and its state route companion, SR 27, head west along 4th Street, a four-lane undivided street. The highway turns north onto Newcastle Street and passes along the edge of the Port of Brunswick. Newcastle Street becomes two lanes at 1st Avenue; US 341/SR 27 turns west onto Prince Street then north onto Bay Street, which becomes a four-lane divided highway immediately to the south of the intersection. The highway parallels Norfolk Southern Railway's Brunswick District north between downtown Brunswick to the east and an industrial area along the East River. At the north end of downtown, US 341 has an oblique intersection with US 25 (Newcastle Street), whose companion route is SR 25 Connector (SR 25 Conn.) and which serves as the main street of downtown Brunswick.