Meadows went into show business as a singer and comedienne after her older sister Jayne Meadows had become established as a dramatic actress. After appearing with Phil Silvers in the road company of "High Button Shoes" and on Broadway in "Top Banana", she was hired as a singer and sketch player on the "Bob and Ray", produced in New York. Across town, Jackie Gleason was looking for a new actress to play Alice in sketches about a working class couple. Pert Kelton, who had been portraying Alice, had been blacklisted in "Red Channels" and could no longer be employed. Meadows was younger and softer than Kelton but her eyes had just the right smoky quality with just a hint of sexuality and Gleason hired her. She joined his variety show doing "The Honeymooners" sketches, winning an Emmy for her work. When the sketches were turned into a regular half-hour series in 1955, Meadows went along, and the 39 episodes produced have become TV classics. Simultaneously, she had been appearing as a panelist on numerous quiz shows. When Gleason returned to a regular variety show format, Meadows briefly remained with him playing the girlfriend of his Reginald Van Gleason before spending several seasons on the panel show "Masquerade Party".
In the early 60s, Meadows tried her hand in features, playing Doris Day's wisecracking roommate in "A Touch of Mink" (1962) and the more progressive wife in "Take Her, She's Mine" (1963). But except for "Rosie" (1967), she devoted herself in the 60s and 70s to occasional guest appearances on episodic TV and game shows. In 1982, Meadows was back on sitcoms as Ted Knight's mother-in-law from hell in the ABC sitcom "Too Close for Comfort". On the short-lived "Uncle Buck" (CBS, 1990), she was cast as the stern grandmother. After Gleason's death in 1987, Meadows appeared on numerous salutes to the star as well as on TV retrospectives. She published her autobiography in 1994, "Love, Alice: My Life as a Honeymooner". Meadows remained loyal to Gleason's memory crediting him with her success. The acerbic ripostes were saved for the cameras, where, preserved forever, America can hear Ralph saying "This is probably the biggest thing I ever got into" and Alice giving him a look and responding, "The biggest thing you ever got into is your pants." Alice could always top Ralph.