Lainie made her Broadway debut in The Happiest Girl in the World in 1961 followed by Bravo Giovanni (1962). She served as understudy to Barbra Streisand in Funny Girl, finally getting to go on 18 months into the run when the star was felled by a serious throat problem. Coincidentally, both had attended the same high school, Erasmus Hall High School in Brooklyn, New York. Kazan's mother alerted the press and, encouraged by rave reviews for her performance, she quit the show and set out to establish herself in a singing career.
As her popularity increased, Kazan posed nude for a spread in the October 1970 issue of Playboy, which was reused in Pocket Playboy #4, issued in 1974. Her appearance in the magazine opened the door for her to headline and operate two different Playboy Jazz Clubs, both under Hugh Hefner's overview, which she called Lainie's Lounge East and West on opposite coasts, one in Los Angeles and the other in Manhattan. Her Playboy photographs also inspired the look of Jack Kirby's DC Comics superheroine Big Barda.
Kazan appeared in numerous supper clubs across the country, and she guested on Dean Martin's variety series 26 times. Other television work includes a recurring role as Aunt Freida on the Fran Drescher sitcom The Nanny and as Kirstie Alley's mother on Veronica's Closet, and guest shots on St. Elsewhere (resulting in an Emmy nomination), The Paper Chase, Touched by an Angel, and Will & Grace. She was also featured in My Big Fat Greek Life, a short-lived series based on the Nia Vardalos hit film My Big Fat Greek Wedding, in which she had also starred alongside Vardalos. She appeared in a scene as the mother of Adam Sandler's character in I Now Pronounce You Chuck and Larry, but it was deleted in the feature film. It is, however, included in the special features on disc.
Kazan returned to Broadway to recreate her film role for the musical adaptation of My Favorite Year, earning a Tony Award nomination for her performance. She completed a stint in The Vagina Monologues. She has also appeared in regional productions of A Little Night Music, Man of La Mancha, Gypsy, Who's Afraid of Virginia Woolf?, Hello, Dolly!, and Fiddler on the Roof, among others. In 1984, she made a guest appearance on the Faerie Tale Theatre episode Pinocchio as Sophia the Blue Fairy.
In recent years, Kazan has performed on concert stages and in Las Vegas and Atlantic City showrooms. She appeared in an episode of Ugly Betty, playing the mother of Bobby, who was soon to become the central character's brother-in-law. Thus, her character was soon to become the mother-in-law of the central character.
- The Journey of Natty Gann (1985)
- Harry and the Hendersons (1987)
- Beaches (1988)
- Eternity (1989)
- Out of the Dark (1989)
- 29th Street (1991)
- I Don't Buy Kisses Anymore (1992)
- The Cemetery Club (1993)
- My Big Fat Greek Wedding (2002)
- Eight Crazy Nights (2002) (voice)