Illinois Route 111 runs along the western edge of South Roxana, leading north to Wood River and south to Pontoon Beach. Downtown St. Louis is to the south-southwest. Illinois Route 255, a four-lane expressway, passes just east of the village limits, with access from Exits 3 and 5. Route 255 leads south to Interstates 255 and 270 and north to Bethalto.
