Born Cameron McDowell Mitzel in Dallastown, Pennsylvania to Rev. Charles and Kathryn Mitzel, young Cameron moved to Chicora, Butler County, Pennsylvania in 1921 when his father was accepted as pastor of the St. John's Reformed Church of Donegal Township, Pennsylvania. Mitchell served as a bombardier with the United States Army Air Forces during World War II.
His film career began with minor roles in films dating back to 1945, including They Were Expendable (with John Wayne and Robert Montgomery), but Mitchell quickly rose to leading man status. He co-starred with Wallace Beery in The Mighty McGurk, with Doris Day and James Cagney in Love Me or Leave Me, with Lana Turner and Spencer Tracy in Cass Timberlane, with Clark Gable and Jane Russell in The Tall Men, with Marlon Brando, Merle Oberon, Jean Simmons in Désirée, and with Joanne Woodward and Sheree North in No Down Payment.
Some of his best known films were the 1951 adaptation of Death of a Salesman (he originated the role of Happy on Broadway), the 1952 version of Les Miserables (as Marius), the 1953 comedy How to Marry a Millionaire (with Marilyn Monroe), and 1956's film version of the stage musical Carousel.
During the 1960s, Mitchell starred in numerous Italian horror, fantasy, and thriller films, several of which were directed by Mario Bava, including Erik the Conqueror (1961), Blood and Black Lace(1964), and Knives of the Avenger (1966). He had a funny role as a '50s gangster in the 1980 comedy My Favorite Year and portrayed right-wing General Edwin A. Walker in Prince Jack (1985).
It was on TV where Mitchell had the greatest effect during the latter part of his career, and he is best remembered for starring as Uncle Buck in the 1960s NBC western series, The High Chaparral. He also made an appearance on an episode of Bonanza and ABC's S.W.A.T. He guest starred on the brief Swiss Family Robinson TV series and the 'Landslide' episode of "Movin' On" in 1975. He appeared on Gene Evans's short-lived Spencer's Pilots on CBS in the fall of 1976. He voiced Jesus of Nazareth in The Robe. He also had roles in horror films such as the 1964 giallo Blood and Black Lace, the 1978 exploitation film The Toolbox Murders, the 1978 creature feature The Swarm the 1979 slasher film The Demon, the 1980 slasher Silent Scream, and the 1987 anthology film From a Whsiper to a Scream.
Between the first and second world wars, during his years as a young actor in Alfred Lunt and Lynn Fontanne's National Theater Company, Fontanne suggested that Cameron's surname sounded "a bit too much like the Hun" and insisted he change it to "Mitchell."
His first and last name were used for the fictional gay couple Mitchell Pritchett (Jesse Tyler Ferguson) and Cameron Tucker (Eric Stonestreet) in the ABC comedy Modern Family.
In 1940, Mitchell married Johanna Mendel, the daughter of self-made Canadian business tycoon Fred Mendel. The Mendel family was based in Saskatoon, Saskatchewan, where Fred Mendel founded Intercontinental Packers, a major family-owned meat packing operation.
Johanna Mitchell gave birth to their first son, Robert Cameron Mitchell, in New York on July 4, 1941. Although Mitchell and Johanna divorced in 1960, he maintained close ties to Canada. His children by Johanna hold dual US/Canada citizenship. Their daughter, Camille Mitchell, and son, Cameron Mitchell, Jr., are both actors. Another son, Fred Mitchell, was president of Intercontinental Packers for many years working alongside his mother, Johanna Mitchell, who was Chairwoman of the Board. Today the company is known as Mitchell's Gourmet Foods and still operates out of Saskatoon, now owned by Maple Leaf Foods.
Mitchell died of lung cancer, aged 75, on July 7, 1994, in Pacific Palisades, California. He is buried in Desert Memorial Park in Cathedral City, California.