George was born in Norwood, Ohio to immigrants from Greece. He made his film debut at the age of 12 singing in the chorus of Song of Love (1947). Following his graduation from high school, he supported his night-time dancing, singing and dramatic lessons with a daytime job clerking in a Los Angeles department store.

For several years he appeared in small roles, usually as a dancer or a member of the chorus in various musical films. He was one of the dancers in Marilyn Monroe's "Diamonds Are a Girl's Best Friend" number in Gentlemen Prefer Blondes (1953) and also appeared as a dancer alongside Rosemary Clooney in White Christmas. He can also be seen in the "Chop Suey" number in the musical film Flower Drum Song.

Performed the role of Riff, leader of the Jets, in the London stage production of "West Side Story" before winning the role of Bernardo, leader of the rival Sharks gang, in the film version (1961). His biggest success came with this film, for which he won the Academy Award for Best Supporting Actor.

He also had a starring role as a doctor in the film Diamond Head opposite Charlton Heston and Yvette Mimieux in 1963. He also acted (along with Gene Kelly) in Jacques Demy's French musical Les Demoiselles de Rochefort (1967).

George has also appeared on Broadway and television. In the early 1960s, he embarked on a career as a pop singer which resulted in a couple of minor hit songs. He hit #110 on the Billboard Hot 100 pop charts with "Maria" in October of 1962.

In 1983, George appeared in "Jekyll and Hyde... Together again" with Mark Blankfield.

He had a recurring role on the popular TV show Superboy as Professor Peterson during the series' first two seasons from 1988-1990. Chakiris last acted in a 1996 episode of the sitcom Last of the Summer Wine and has given occasional television interviews since then. He is mostly retired and has taken up jewelery making as an occupation.