She was born in Halifax, Nova Scotia, Canada, in 1909 (although some sources, including (]) have indicated the year was 1910), of Irish Catholic extraction. She was the sister of minor actresses, Helen Keeler and Gertrude Keeler.

Three years later, her family packed up and moved to New York City. There were six children, so although Keeler was interested in taking dance lessons, the family simply could not afford to.

Keeler attended a parochial school on the East Side of New York City, and one period per week, a dance teacher would come and teach all styles of dance. The teacher saw potential in Keeler and spoke to her mother about Ruby taking lessons at her studio. Although her mother declined, apologizing for the lack of money, the teacher wanted to work with her so badly, that she asked her mother if she would bring her to a class lesson on Saturdays, and she agreed.

During the classes, a girl she danced with told her about auditions for chorus girls. The law said you had to be 16 years old, and although they were only 13, they decided to lie about their ages at the audition. It was a tap audition, and there were a lot of other talented girls there. The stage was covered, except for a wooden apron at the front. When it was Ruby's turn to dance, she asked Julian Mitchell, the dance director for the show, if she could dance on the wooden part so that her taps could be heard.

He did not answer, so she went ahead, walked right up to the front of the stage, and started the routine there. He said, "who said you could dance up there?" She replied, "I asked you!" and got a job in George M. Cohan's The Rise of Rosie O'Reilly in 1923, in which she made forty-five dollars a week to help her family.

During her days at Texas Guinan's nightclub, Keeler met legendary entertainer Al Jolson. The couple began dating and wed in 1928; she was 19 and he was 42. Alas, the marriage (during which they adopted a son) was a rocky one and the couple divorced in 1940. Keeler remarried in 1941 to John Homer Lowe, and they had four children; Lowe died of cancer in 1969.

In 1933, producer Darryl F. Zanuck cast Keeler in the Warner Bros. musical 42nd Street opposite Dick Powell and Bebe Daniels. The film was a huge success due to the innovative Busby Berkeley's lavish choreography. As a result of her performance in 42nd Street, Jack L. Warner gave Keeler a long-term contract and cast her in such hits as Gold Diggers of 1933 (1933) and Dames (1934).

Not anxious to be a movie star, and happy in her second marriage, Keeler left show business in 1941, and went on to raise five children. In 1971, she came out of retirement to star in the hugely successful Broadway revival of No, No, Nanette, along with fellow Irish-Americans Helen Gallagher and the late Patsy Kelly. The production was directed by Keeler's 42nd Street director, Busby Berkeley.

Ruby Keeler was the first tap dancing star of motion pictures. She was a Buck dancer. Both the shoes and the style were different from regular tap dance. Instead of metal taps, the soles were wooden, and hard. Buck dancers stayed in relatively the same place on stage, and their concern was the rhythm coming from their feet, rather than how they looked on stage. They stayed on the balls of their feet most of time, which meant that their torsos moved very little, and the movements were isolated to below the waist. Because of this style of movement, the early Buck dancers often appeared less graceful in comparison with later tap dancers.

Ruby Keeler died of cancer in Rancho Mirage, California at the aged either 82 or 83, and was interred in the Holy Sepulcher Cemetery in Orange, California. She has a Star on the Hollywood Walk of Fame at 6730 Hollywood Blvd.