The son of opera singers (his father was the first black man to perform regularly with the Metropolitan Opera), McFerrin was born in New York City. In 1958 his family moved to Los Angeles. McFerrin attended Sacramento State University and Cerritos College, but dropped out to play piano for the Ice Follies. Over the next few years, he played keyboard with lounge acts and for dance troupes. In 1977 McFerrin decided, suddenly, to become a singer. "I was in a quiet moment when a simple thought just came into my head: ‘Why don’. you sing?’ It was as simple as that, but it must have had some force behind it because I acted on it immediately," he explained to Bourne. He sang with various bands and was eventually discovered by singer Jon Hendricks. While on tour with Hendricks, McFerrin was again discovered - this time by comedian Bill Cosby.
As a vocalist, McFerrin often switches rapidly between modal and falsetto registers to create polyphonic effects, performing both the main melody and the accompanying parts of songs. He makes use of percussive effects created both with his mouth and by tapping on his chest. McFerrin is also capable of multiphonic singing.
A document of McFerrin's approach to singing is his 1984 album The Voice, the first solo vocal jazz album recorded with no accompaniment or overdubbing.
McFerrin's song "Don't Worry, Be Happy" was a No. 1 U.S. pop hit in 1988 and won Song of the Year and Record of the Year honors. McFerrin has also worked in collaboration with instrumental performers, including pianists Chick Corea, Herbie Hancock, and Joe Zawinul, drummer Tony Williams, and cellist Yo-Yo Ma.