Born Charles Joseph Parrott, Jr. in Baltimore, Maryland, Chase started his career in films by working at the Christie Comedies in 1912. He then moved to Keystone Studios where he began appearing in bit parts in the Mack Sennett films, including those of Charles Chaplin.

In 1920, he began working as a film director for Hal Roach Studios; among his notable early works for Roach was supervising the first entries in the Our Gang series. He eventually moved back in front of the camera with his own series of shorts, adopting the screen name Charley Chase. Direction of the Chase series was soon taken over by Leo McCarey, who in collaboration with Chase formed the comic style of the series-- an emphasis on situation comedy, characterization, and farce instead of knockabout slapstick. From the start of his series until his death, Chase remained the guiding hand behind the films, acting as director, writer, and editor (though he only began to receive director's credit at Roach in 1933 as Charles Parrott.) Some of Chase's starring shorts of the 1920s, particularly Mighty Like a Moose, Fluttering Hearts, and Limousine Love, are among the finest in the silent comedy genre.

Charley Chase moved with ease into sound films in 1929 and continued to be quite prolific, occasionally putting his fine singing voice on display and including his self-penned songs in his comedy shorts. Chase's The Pip From Pittsburg, produced in 1931, is one of the most celebrated Hal Roach comedies of the 1930s. Throughout the decade, the Charley Chase shorts continued to stand alongside Laurel and Hardy and Our Gang as the core output of the Roach studio. Chase appeared on-screen with Laurel and Hardy a number of times, and co-starred in their 1933 feature film Sons of the Desert. Chase's failure to adapt to the feature film format was primarily responsible for his dismissal from the Hal Roach Studio in 1936.

In 1937, Chase began working at Columbia Pictures, where he spent the rest of his career continuing to star in his series of comedies as well as directing other Columbia personalities, such as The Three Stooges. Chase's tumultuous, fast-living lifestyle (he suffered from alcoholism for most of his professional career) began to take a serious toll on the comedian's health. Though still often producing quality comedies - such as one of his last, The Heckler, which is considered to be one of his best talkies - Chase's physical decline could not be ignored when viewing his work from the late 1930s.

Charley Chase died of a heart attack in California in 1940 and was interred in the Forest Lawn Memorial Park Cemetery in Glendale, California.