Mix worked as a cowhand in Texas, Arizona, Wyoming, and Montana and served in the U.S. Army in the Spanish-American War and in the pursuit of Pancho Villa during the Mexican Revolution. He was also a deputy sheriff in Oklahoma and served in the Texas Rangers. In 1906 he joined a Wild West show and, three years later, the Sells-Floto Circus. He began to act in motion pictures in 1910, playing the part of a roughriding hero, defender of right and justice. Over the years his horse “Tony” became almost as famous as Mix himself. Mix appeared in more than 200 one- and two-reelers and feature films, many of which he also produced or directed.

After gaining riches and worldwide fame during the silent era, Mix suffered a decline with the coming of sound, appearing in only a few pictures after 1929. In 1933 he organized Tom Mix's Circus and Wild West Show, but, by the time of his death in an automobile accident seven years later, his wealth had largely disappeared.