Born to Fred and Bertha Rogers Simpson, his paternal heritage was Irish. He was the eldest of four sons, one of whom, Richard, died in childhood. When his father, a contractor, was unable to work following the 1929 stock market crash, his mother supported the family as a waitress.

By his twenties, Simpson had grown into a hulking figure and considered a boxing career. He has been referred to in some sources as the 1935 "New York City Heavyweight Boxing Champion," but the only official records of his ring work are for two fights in Los Angeles in 1939, both of which he lost. Simpson, nicknamed "Mickey," arrived in Los Angeles in the late 1930s. Some unconfirmed stories have him working as a chauffeur for Claudette Colbert. In 1939, he reportedly played a tiny bit part in his first film, Stagecoach. The Director, John Ford, would loom large in Simpson's career.

Simpson found fairly steady movie work as various guards, cops, bouncers, and thugs until his career was interrupted by World War II, in which he served in the United States Navy as a Shore Patrolman, keeping drunken sailors and townies from killing each other, while patrolling the many L.A. bars and strip clubs. When he returned to Hollywood, it was Ford who resurrected his career, giving Simpson a small but notable role as one of Walter Brennan's sons in My Darling Clementine. Simpson would appear in a total of nine Ford films. He appeared in episode 117 of the TV Series The Lone Ranger in 1953 and episode 141 in 1954. During the late 1950s he portrayed the role of Boley on the television series Captain David Grief.

Simpson worked, primarily in lesser roles, until his late 50s. He died from heart failure in Northridge, California on September 23, 1985, at the age of 71. He was buried at Forest Lawn, Hollywood Hills Cemetery in Los Angeles.