He received an undergraduate degree from Chicago Musical College in 1946, then moved to New York. In 1949, he appeared in William Grant Still's Troubled Island at New York City Opera and as Amonasro in Aida with the National Negro Opera Company. He joined the New England Opera Company in 1950.
In 1953, McFerrin won the Metropolitan Opera national auditions and became the first black male to join the company. He made his debut in 1955 as Amonasro, three weeks after contralto Marian Anderson became the first black to sing a principal role at the Met. His other roles at the house were Valentin (in Gounod's Faust) and Rigoletto.
McFerrin also sang the role of Porgy (played onscreen by Sidney Poitier) in the soundtrack of the 1959 film of Gershwin's Porgy and Bess. He toured internationally as a recitalist and was also active as a teacher.
McFerrin moved back to St. Louis in 1973. He suffered a stroke in 1989 that hindered his ability to speak, according to the AP, but he continued to sing for many years after that. Doctors suspected he had Alzheimer's disease in 2003.
The AP quotes Opera Theatre of Saint Louis general director Charles MacKay describing McFerrin's voice as "beautiful, virile, strong, and sensitive ... He sang with such joy and commitment. It reminds me of the profound pleasure of a beautifully trained singing voice."
McFerrin Sr. performed together with his famous son Bobby and the St. Louis Symphony in 1993, father as vocal soloist and son as conductor. McFerrin's daughter, Brenda McFerrin, is also a recording artist.
Speaking about his father, Bobby McFerrin told the AP in a 2003 interview, "His work influenced everything I do musically. When I direct a choir, I go for his sound. His musical influence was absolutely profound. I cannot do anything without me hearing his voice."