He worked as an extra, stunt man and bit player from 1927-28, when he signed a contract with MGM, where he was cast in a major role in The Jazz Age (1929), and got his first leading role that same year in The Silver Horde. He moved to RKO in 1930, where he established himself as a handsome leading man who was considered versatile enough to star in both dramas and comedies.

McCrea graduated from Hollywood High School and then Pomona College (class of 1928), where he had acted on stage and took courses in drama and public speaking, while appearing regularly at the Pasadena Playhouse. As a high school student, he worked as a stunt double and held horses for Cowboy stars william S. Hart and Tom Mix.

According to David Ragan's Stars of the '30s, the McCreas were prodigious savers, accumulating a large estate, which included working-ranch properties. Joel McCrea's work ethic was in part attributed to his Scottish heritage and it also may have stemmed from his friendship in the 1930s with fellow personality and sometime actor Will Rogers. McCrea recounted that "the Oklahoma Sage" gave him a profound piece of advice: "Save half of what you make, and live on just the other half."

McCrea married Actress Frances Dee in Brooklyn on October 20, 1933, after they met while filming The Silver Cord. The couple had three sons, David, who became a rancher; Peter, who became a real estate developer; and Jody, who became an actor. Joel and Frances remained married until his death — spending 57 years together.

In 1934, he made his first appearances with two leading ladies he would be paired with often: with Miriam Hopkins he made The richest Girl in the World, the first of their five films together, and with Barbara Stanwyck he appeared in Gambling Lady, the first of their six films.

Later in the decade, he was the first actor to play "Dr. Kildare", in the film Internes Can't Take Money (1937), and he starred in two large-scale Westerns, Wells Fargo (1937) with his wife Frances Dee, and Cecil B. DeMille's Union Pacific (1939).

By the end of the 1940s, McCrea was a multi-millionaire, as much from his real-estate dealings as from his movie stardom. In the late 1960s, he sold 1,200 acres (4.9 km) of land to an oil company, on the condition that they would not drill within sight of his home.

McCrea also starred in two william A. Wellman westerns, The Great Man's Lady (1942), again with Stanwyck, and Buffalo Bill (1944), with character actor Edgar Buchanan and a young Maureen O'Hara. After the success of The Virginian in 1946, McCrea made Westerns exclusively for the rest of his career, with the exception of the British-made Rough Shoot (1953).

In the early 1950s, McCrea starred as Jace Pearson on the radio series western, Tales of the Texas Rangers.

In 1959, McCrea and his son Jody starred in the NBC-TV series Wichita Town, which lasted only one season. A few years later, McCrea united with fellow veteran of westerns Randolph Scott in Ride the High Country (1962), directed by Sam Peckinpah, after which he did not make another feature film until The Young Rounders (1966). Four more years were to pass before his next film, but 1970 saw the release of two films: Cry Blood, Apache, again with his son Jody, and Sioux Nation. He made his final film appearance in 1976, in Mustang Country.

In 1968, McCrea received a career achievement award from the L.A. Film Critics Association, and the following year he was inducted into the Western Performers Hall of Fame at the National Cowboy & Western Heritage Museum in Oklahoma City, Oklahoma.

Performing in Westerns was a return to what he had done earlier in his career, and McCrea enjoyed the genre. In a 1978 interview, he said:

Joel McCrea made his final public appearance on October 3, 1990, at a fundraiser for Republican gubernatorial candidate Pete Wilson in Beverly Hills. He died less than three weeks later, on October 20, at the Motion Picture & Television Country House and Hospital in Woodland Hills, California from pneumonia, at the age of 84.

McCrea – who was an outdoorsman who had once listed his occupation as "rancher" and his hobby as "acting" – had begun buying property as early as 1933, when he purchased his first 1,000 acres (4.0 km) in a then unincorporated area of eastern Ventura County, California, which later became Thousand Oaks, California. This was the beginning of what became a 3,000-acre (12 km) spread on which McCrea and his wife Frances lived, raised their sons, and rode their horses.