A daring gang of outlaws hijack a carload of raw silk from a speeding freight train, then split into three trucks, meeting in the distant town of Cosmopolitan. After one truck skids into a ditch, the gangsters flag down a truck carrying three saddle horses, holding up The Three Mesquiteers: "Stony" Brooke, "Tucson" Smith, and "Lullaby" Joslin. The robbers load the silk onto the Mesquiteers' truck, taking it and the trio with them.
Call the Mesquiteers
A trio of outlaws steal the Mesquiteers' truck, leading to a mix-up where the authorities mistakenly believe the Mesquiteers are part of the gang. As a result, the Mesquiteers must go into hiding and prove their innocence while being relentlessly pursued as fugitives.