Curtis grew up in an impoverished section of the Bronx, and had joined a street gang by the age of eleven. He joined the Navy in 1943, and after the war, attended the City College of New York and took acting lessons at the Dramatic Workshop. In 1948 he moved to California and was placed under contract by Universal Studios, making his screen debut in "Criss Cross" (1948). Soon afterward, his good looks made him a matinee idol, initially under the name James Curtis, and then Anthony Curtis.

Curtis sought work in a variety of genres in order to avoid being typecast. His first major film was "The Sweet Smell of Success" (1957). He was nominated for an Academy Award for his performance in "The Defiant Ones" (1958). He demonstrated his comedic talent in Billy Wilder's classic "Some Like It Hot" (1959) with Marilyn Monroe and Jack Lemmon.

Curtis enjoyed a close friendship with Hollywood's "Rat Pack", a group of entertainers which included Frank Sinatra, Dean Martin, Sammy Davis, Jr., Joey Bishop and Peter Lawford. He appeared in several films with Rat Pack members, including "Pepe" (1960) and "The List of Adrian Messenger" (1963).

Despite a cardiac bypass operation in 1994, Curtis occasionally plays supporting roles in films, whilst enjoying a successful second career as a fine artist.

Curtis has been married five times. He wed actress Janet Leigh in 1951, and the couple had two daughters, Kelly Lee and Jamie Lee. Curtis and Leigh split in 1962, after which Curtis married actress Christine Kaufmann. They had two daughters, Alexandrea and Allegra. Curtis and Kaufmann divorced in 1967. He married Leslie Allen in 1968 and they had two sons: Nicholas and Benjamin. Curtis and Allen divorced in 1982. He wed lawyer Lisa Deutsch in 1993, and divorced her in 1994. He married fifth wife Jill Vanden Berg on November 6, 1998.