Born and raised in Dothan, Alabama, Brown was a star of the high school football team, earning a football scholarship to the University of Alabama. Playing the halfback position on his university's Crimson Tide football team, Brown helped his team to become the 1926 NCAA Division I-A national football champions. In that year's Rose Bowl, he scored two of his team's three touchdowns in an upset win over the favored Washington Huskies.

His good looks and powerful physique saw him portrayed on Wheaties cereal boxes and in 1927, brought an offer for motion picture screen tests that resulted in a long and successful career in Hollywood. He appeared in minor roles until 1930 when he was cast as the star in a western movie titled Billy the Kid directed by King Vidor.

After a few more films, Brown returned to making exclusively westerns and eventually became one of the screen's top cowboy stars, making 127 western films during his career. Brown also starred in four serials for Universal Studios and was a hero to millions of young children at movie theaters and on their television screens. When the western genre experienced a sharp drop in box office popularity, Johnny Mack Brown went into retirement in 1953. He returned more than ten years later to appear in secondary roles in a few western style films.

In recognition of his contribution to the motion picture industry, Brown was given a star on the Hollywood Walk of Fame at 6101 Hollywood Blvd.

Johnny Mack Brown died in Woodland Hills, California of heart failure at the age of 70. He was interred in the Forest Lawn Memorial Park Cemetery in Glendale, California.

See also: Other notable figures in Western films