Stritch was born to a wealthy, devoutly Roman Catholic family, and is the niece of the late Samuel Cardinal Stritch, Archbishop of Chicago. She trained at the Dramatic Workshop of the New School for Social Research in New York City under Erwin Piscator; other students at the Dramatic Workshop included Marlon Brando and Bea Arthur. Her Broadway debut came in the revue Angel in the Wings. Stritch was standby to Ethel Merman for the Irving Berlin musical Call Me Madam while simultaneously singing the song "Zip" in the 1952 revival of Pal Joey. Stritch later starred in the national tour of Call Me Madam.

She has been successful in Broadway musicals, such as Sail Away by Sir Noel Coward, Company by Stephen Sondheim, and the most recent musical revival of Show Boat, which also starred Lonette McKee and John McMartin.

Once a very heavy drinker, she became a teetotaler after being diagnosed with diabetes.

She played the first Trixie Norton, the burlesque dancing wife of Art Carney's Ed Norton, on Jackie Gleason's first Honeymooners sketch on television, but was replaced by the less glamorous-looking, but more wholesome Joyce Randolph the following week.

She is best known for her stage work, having been nominated for the Tony Award four times:

Best Featured Actress in a Play for Bus Stop, 1956 Best Actress in a Musical for Sail Away, 1962 Best Actress in a Musical for Company, 1971 Best Actress in a Play for A Delicate Balance, 1996 In 1972, she moved to London, England to star in the West End production of Company. She stayed in London to work on stage and in British television, having married a younger Canadian actor named John Bay; their happy marriage ended when Bay died of brain cancer in 1982. For ITV she appeared in the BBC television series Two's Company with Sir Donald Sinden. After her husband's death, Stritch returned to the US.

In 2002, her one woman show Elaine Stritch at Liberty won the Tony for Best Special Theatrical Event. The show itself, in addition to the rehearsal process and Stritch's backstage struggles with, among other things, alcoholism and diabetes, are documented in the D.A. Pennebaker film of the same name.

The film went on to win several Emmy Awards, including Outstanding Individual Achievement in a Variety or Music Program for Stritch, who famously quipped, "I know that most of you who just won an award are thinking 'Hah! I'm glad I won and you didn't!'".

She has made many cameo appearances in films, such as Woody Allen's Small Time Crooks. She was reportedly also considered to play Bea Arthur's role of Dorothy on The Golden Girls, but, by her own admission, offended the producers by improvising profanity into the script. She is good friends with gossip columnist Liz Smith (journalist), and they share the same day of birth February 2, albeit 2 years apart.

She is spoofed in the Forbidden Broadway songs "The Ladies Who Screech" and "Stritch", parodies of "The Ladies Who Lunch" and "Zip", songs she performed in the musicals Company and Pal Joey, respectively.