Produced by Jack Schwartz for low-budget company Screen Guild, this mild Western starring the veteran Richard Arlen was apparently the first entry in a proposed series. Arlen played the title role, here assigned by the army to quell an Indian attack on the powerless settlers. The Indians are accusing Tom Russell (John Dexter) of murdering a member of the tribe, an act, as Buffalo Bill discovers, actually committed by a gang of outlaws hired by investment company owner J.B. Jordon (Frank O'Connor). Buffalo Bill Rides Again was soundly defeated by a low budget and slipshod direction by the veteran Bernard B. Ray. Popular B-Western villain Ted Adams disappeared mysteriously halfway through the film, only to be replaced by Edmund Cobb. Jennifer Holt, the daughter of Arlen contemporary Jack Holt and by far the busiest B-Western heroine of the 1940s, had little to do other than letting herself be kidnapped by evil Gil Patric.

Buffalo Bill est désigné par le gouvernement pour régler un conflit opposant des financiers avides de s'approprier indûment, par la force, des terrains pétrolifères à des fermiers, propriétaires des terres. Sur place Buffalo Bill devra s'attaquer à une autre injustice : un fermier est accusé d'avoir assassiné un indien. Bill pourchassera le coupable avec l'aide d'autres peaux-rouges.