In 1933 Ralston-Purina obtained his permission to produce a Tom Mix radio series called Tom Mix Ralston Straight Shooters which, but for one year during World War II, was popular throughout most of the 1930s through the early 1950s. Mix never appeared on these broadcasts and was instead played by radio actors: Artells Dickson (early 1930s), Jack Holden (from 1937), Russell Thorsen (early 1940s) and Joe "Curley" Bradley (from 1944). Others in the supporting cast included George Gobel, Harold Peary and Willard Waterman.The Ralston company offered ads during the Tom Mix radio program for listeners to send in for a series of 12 special Ralston-Tom Mix Comic books available only by writing the Ralston Company by mail.

On the afternoon of October 12, 1940, Mix was driving his 1937 Cord 812 Phaeton near Florence, Arizona, (between Tucson and Phoenix) on Arizona State Route 79. Mix had been visiting Pima County Sheriff Ed Nichols in Tucson and had stopped at The Oracle Junction Inn, a popular gambling and drinking establishment, where he had called and spoken with his agent, when he came upon construction barriers at a bridge previously washed away by a flash flood. A work crew watched as he was unable to brake in time and his car swerved twice then rolled into a gully, pinning his body beneath.