Buffalo Bill and Wild Bill Hickok join forces to establish a mail route that can get mail from St. Joseph, Missouri, to Sacramento, California, in ten days. Along the way they must battle bad weather, hostile Indians and outlaws intent on robbing the mail and shutting down the entire operation.

Charlton Hestonas Captain William Frank 'Buffalo Bill' Cody
Rhonda Flemingas Evelyn Hastings
Jan Sterlingas Denny Russell
Forrest Tuckeras James Butler aka Wild Bill Hickok
Porter Hallas Jim Bridger
Henry Brandonas Joe Cooper
Richard Shannonas Red Barrett
Stuart Randallas Pemberton
Lewis Martinas Sgt. Russell
Pat Hoganas Chief Yellow Hand (uncredited)