Produced by Milton Sperling's United States Pictures, South of St. Louis was given a widespread release by Warner Bros. The story begins in the last days of the Civil War. Chased off their property by guerillas, ranching partners Kip Davis (Joel McCrea), Charlie Burns (Zachary Scott) and Lee Prince (Douglas Kennedy) head southward to seek out a new life. Davis and Burns go into the gun-running business, while Prince joins the Confederate Army. Kip and Charlie battle over the affections of saloon gal Rouge de Lisle (Alexis Smith), a turn of events that falls into the plans of rival gunrunner Luke Cottrell (Victor Jory). The three former friends soon find themselves enemies, and thereby hangs the plotline. Curiously, Dorothy Malone, cast as the "good" heroine, seems to be more worldly and cunning than hard-boiled temptress Alexis Smith.