Born in Onset Bay, Massachusetts, Farrell began his career in Hollywood taking bit parts in the early 1920s. His first film appearance was in an uncredited role in the 1923 film The Cheat starring the Polish-born screen vamp Pola Negri and actor Jack Holt. Farrell's second film role was in the enormously popular Wallace Worsley directed 1923 film adaptation of the Victor Hugo novel The Hunchback of Notre Dame, starring Lon Chaney

Farrell continued to work throughout the 1920s in relatively minor roles without much success until the 1927 onscreen pairing with actress Janet Gaynor in the romantic drama Seventh Heaven. The film was an enormous public and critical success and Farrell and Gaynor would go on to star opposite one another in over twelve films together throughout the late 1920s and into the talkie era of the early 1930s. Unlike many of his silent screen peers, Farrell had little difficulty with "voice troubles" and remained a publicly popular actor throughout the sound era.

During the early 1950s, after his career in motion pictures began to slow, Farrell began appearing on the popular television series My Little Margie. The series ran from 1952 to 1955 and Farrell starred opposite actress Gale Storm. In 1956 Farrell hosted in his own television program, The Charles Farrell Show.

Farrell married the popular film acress Virginia Valli on February 14, 1931 and the couple were married until Valli's death on September 24, 1968.

After retiring from his acting career, Farrell became a lifelong resident of Palm Springs, California and opened the popular Palm Springs Racquet Club in the city with fellow actor Ralph Bellamy. A major factor in the prosperity of Palm Springs in the 1950s, Farrell was elected mayor of the community in 1953, a position he held for seven years. Farrell died from a heart attack in 1990 at the age of 89 and was interred at the Welwood Murray Cemetery in Palm Springs.

For his contribution to both motion pictures and television, Charles Farrell was awarded two stars on the Hollywood Walk of Fame in Hollywood, California at the following locations: 7021 Hollywood Blvd. (motion pictures), and 1617 Vine Street (television).