Castle was born to Erby G. Noblett, Sr. and Myrtle A. Noblett (née Brown) in Pampa, Texas. Her mother was one-sixteenth Quapaw Indian. The Nobletts moved to Fort Worth, Texas, then Phillips, subsequently a ghost town in Hutchinson County, Texas, prior to relocating to Long Beach, California. At the age of nine, Castle contracted pneumonia. Her brother, Erby Noblett, Jr. (1927–1992), taught her trick riding and later became a police officer in Long Beach.

Castle gave birth to an out-of-wedlock daughter in Los Angeles in 1946.

Castle's first credited role was as Flo in the 1950 film The Tougher They Come. Columbia plotted Castle's career as it had for Rita Hayworth when she had first signed with Columbia: frequent exposure and seasoning in the studio's low-budget films. Most of Mary Castle's early Columbias were Westerns: Prairie Roundup, Texans Never Cry (with Gene Autry), and When the Redskins Rode. With an obvious resemblance to Hayworth, she was seen as the object of soldiers' dreams in Columbia's 1952 war film Eight Iron Men.

Mary Castle's first television appearance occurred in 1952 as Marcia Thorne in the episode "One Angle Too Many" of the detective series Racket Squad. She appeared with Jim Davis in 26 of the 39 episodes of Stories of the Century, the first western to win an Emmy Award. The series focuses upon the capture of such western outlaws as Billy the Kid, the Dalton Brothers, the Younger Brothers, and Sam Bass. When Castle left the series, she was replaced for the final thirteen episodes by Kristine Miller.

Her appearance in Criminal Lawyer didn't free Castle from the Western mold; In 1953, she appeared in the Western features The Lawless Breed and Gunsmoke. The most frequently revived Mary Castle feature is probably her least prestigious: she played a gold-digging femme fatale opposite Huntz Hall and The Bowery Boys in the low-budget comedy Crashing Las Vegas (1956). She was only 24 when it was filmed, but looked years older; a new blonde hairstyle didn't disguise her now-hardened features from alcohol abuse.

In 1956, she appeared on The Bob Cummings Show in the episode "The Trouble with Henry". In 1957, she guest starred on ABC's The Adventures of Ozzie and Harriet, in "The Case of the Baited Hook" on CBS's Perry Mason, and in "Test of Courage" of ABC's Cheyenne, starring Clint Walker. She appeared too in Frank Lovejoy's detective series, Meet McGraw.

Castle was involved romantically with several men, including actor Richard Long. She ultimately had three short-lived marriages. From 1957 to 1958 she was married to william France Minchen, who used the stage name william Grant; they divorced, and he remarried. From 1960 to 1961 Castle was married from to Wayne Cote. Castle and her third husband, Erwin A. Frezza, were married from 1971 to 1972.

Castle was arrested for public intoxication in December 1957 after she allegedly attempted to kick and bite two deputy sheriffs, John Aiken and K. H. Smiley, in Hollywood. The officers said that they found Castle fighting with her husband in a parked car while her ten-year-old daughter cried in the back seat. On September 14, 1959, Castle was revived by artificial respiration and taken to Malibu Emergency Hospital after being found seemingly lifeless and wearing little clothing on the beach in Malibu. On October 28, 1959, she was arrested again and fined for drunkenness. A month later on November 26, she tried to hang herself upon being placed in a Beverly Hills jail.