[3] McFerrin has also worked in collaboration with jazz fusion instrumentalists including pianists Chick Corea (of Return to Forever), Herbie Hancock (of The Headhunters), and Joe Zawinul (of Weather Report), drummer Tony Williams, and cellist Yo-Yo Ma.

[4] His mother Sara (Copper) McFerrin was a soloist and taught voice at Fullerton College in Southern California.

[8] In 1984, McFerrin performed at the Playboy Jazz Festival in Los Angeles as a sixth member of Herbie Hancock's VSOP II, sharing horn trio parts with the Marsalis brothers.

[9] In 1988, McFerrin recorded the song "Don't Worry, Be Happy", which became a hit and brought him widespread recognition across the world.

Also in 1989, he formed a ten-person "Voicestra" which he featured on both his 1990 album Medicine Music and in the score to the 1989 Oscar-winning documentary Common Threads: Stories from the Quilt.

Around 1992, an urban legend began that McFerrin had committed suicide; it has been suggested that the false story spread because people enjoyed the irony of a man known for the positive message of "Don't Worry, Be Happy" suffering from depression in real life.

In addition to his vocal performing career, in 1994, McFerrin was appointed as creative chair of the Saint Paul Chamber Orchestra.

[14] In McFerrin's concert appearances, he combines serious conducting of classical pieces with his own vocal improvisations, often with participation from the audience and the orchestra.

[18][19][14] In an interview with Daniel Levitin, McFerrin revealed that he had been diagnosed with Parkinson's disease, prompting him to sell his home in rural Pennsylvania and move to San Francisco.

[20] 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.