Wrongly accused of stealing money from a Widows and Orphans fund, Captain Jim Wynnegate flees England in disgrace and sails off to start a new life in the Wild Western frontier of America. He leaves behind the woman he secretly loves, Lady Diana, because he would rather bear the burden of the family disgrace than tell her the truth - that her husband Sir Henry, Jim's back-stabbing cousin, is the real thief. The new world welcomes him without judgment and soon Wynnegate is a successful ranch-owner with a beautiful Indian wife, Nat-U-Rich, and a son. When cattle rustler Cash Hawkins attacks Jim, Nat-U-Rich rescues her husband, killing the outlaw in the process. Charged with murder for the death, the disconsolate squaw commits suicide. Into the ruins of Jim's second shattered life steps Lady Diana, with news that could reconcile the devastated man with his ignoble past.

The Squaw Man was written, produced and directed by Cecil B. De Mille and was reported to be the first feature length film shot in Hollywood. He had gone west to avoid the powerful east coast Motion Picture Patents Trust, headed by Thomas A. Edison, who didn't hesitate to resort to violence in his bid to control all motion picture production. De Mille actually shot two later remakes of The Squaw Man (1918, 1931) and would go on to create such classics as Reap the Wild Wind, The Greatest Show on Earth and The Ten Commandments.