Bailey was born in Southampton County in southeastern Virginia, to Joseph and Ella Mae Ricks Bailey. She was reared in the Bloodfields neighborhood of Newport News, Virginia.  She made her stage-singing debut when she was 15 years old. Her brother Bill Bailey was beginning his own career as a tap dancer, and suggested she enter an amateur contest at the Pearl Theatre in Philadelphia. She entered the amateur song and dance contest and won and was offered $35 a week to perform there for two weeks but the theatre closed during her engagement and she wasn’t paid. She later won a similar contest at Harlem’s famous Apollo Theater, and decided to pursue a career in entertainment.  Bailey began by singing and dancing in Philadelphia’s black nightclubs in the 1930s, and soon started performing in other parts of the East Coast. In 1941, during World War II, Bailey toured the country with the USO, performing for American troops. After the tour, she settled in New York. Her solo successes as a nightclub performer were followed by acts with such entertainers as Cab Calloway and Duke Ellington. In 1946, Bailey made her Broadway debut in St. Louis Woman. Bailey continued to tour and record albums in between her stage and screen performances. Early in the television medium, Bailey guest starred on CBS’s Faye Emerson’s Wonderful Town.

Her support of female impersonator Lynne Carter led him to credit Bailey with launching his career.  In 1954, she took the role of Frankie in the film version of Carmen Jones, and her rendition of “Beat Out That Rhythm on the Drum” is one of the highlights of the film. She also starred in the Broadway musical House of Flowers. In 1959, she played the role of Maria in the film version of Porgy and Bess, starring Sidney Poitier and Dorothy Dandridge. Also that year, she played the role of “Aunt Hagar” in the movie St. Louis Blues, alongside Mahalia Jackson, Eartha Kitt, and Nat King Cole. Though she was originally considered for the part of Annie Johnson in the 1959 film Imitation of Life, the part went to Juanita Moore, for which Moore received an Academy Award nomination.  In 1967, Bailey and Cab Calloway headlined an all-black cast version of Hello, Dolly! The touring version was so successful, producer David Merrick took it to Broadway where it played to sold-out houses and revitalized the long running musical. Bailey was given a special Tony Award for her role and RCA made a second original cast album. That is the only recording of the score to have an overture which was written especially for that recording.  A passionate fan of the New York Mets, Bailey sang the national anthem at Shea Stadium prior to game 5 of the 1969 World Series, and appears in the Series highlight film showing her support for the team. She also sang the national anthem prior to game 1 of the 1981 World Series between the New York Yankees and Los Angeles Dodgers at Yankee Stadium.

During the 1970s she had her own television show, and she also provided voices for animations such as Tubby the Tuba (1976) and Disney’s The Fox and the Hound (1981). She returned to Broadway in 1975, playing the lead in an all-black production of Hello, Dolly! She earned a B.A. in theology from Georgetown University in Washington, D.C., in 1985, at age 67.  Later in her career, Bailey was a fixture as a spokesperson in a series of Duncan Hines commercials, singing “Bill Bailey (Won’t You Come Home)”.  In her later years Bailey wrote several books: The Raw Pearl (1968), Talking to Myself (1971), Pearl’s Kitchen (1973), and Hurry Up America and Spit (1976). In 1975 she was appointed special ambassador to the United Nations by President Gerald Ford. Her last book, Between You and Me (1989), details her experiences with higher education. On January 19, 1985, she appeared on the nationally-televised broadcast of the 50th Presidential Inaugural Gala, the night before the second inauguration of Ronald Reagan. In 1988 Bailey received the Presidential Medal of Freedom from President Reagan.

On November 19, 1952, Bailey married jazz drummer Louie Bellson in London. They adopted a child, Tony, in the mid-1950s, and subsequently a girl, Dee Dee J. Bellson, born April 20, 1960. Tony Bellson died in 2004, and Dee Dee Bellson, at age 49, died July 4, 2009, five months after her father, Louie Bellson, who died on Valentine’s Day 2009.  Bailey, a Republican, was appointed by President Richard Nixon as America’s “Ambassador of Love” in 1970. She attended several meetings of the United Nations and later appeared in a campaign ad for President Gerald Ford in the 1976 election.  She was awarded the Bronze Medallion (New York City award) in 1968 and a Presidential Medal of Freedom on October 17, 1988.  Pearl Bailey died at Thomas Jefferson University Hospital in Philadelphia on August 17, 1990. Following an autopsy, Dr. Emanuel Rubin, professor and chairman of the Department of Pathology at Jefferson Medical College, announced the cause of death as arteriosclerotic coronary artery disease with significant narrowing of the coronary artery. She is buried at Rolling Green Memorial Park in West Chester, Pennsylvania.