Johnny O'Neal was born in Detroit on October 10, 1956, and came up playing gospel piano in the city's churches. He is largely self-taught. In 1974, at seventeen, he left Michigan for Birmingham, Alabama, and turned professional there, working with local players including bassist Cleveland Eaton and pianist Ray Reach. Birmingham claimed him for good: the Alabama Jazz Hall of Fame inducted him in 1997, and he was still going back to sit in with the city's SuperJazz Big Band in 2006, three decades after he first arrived.

The seven years he spent in the South put him on record before New York ever heard him. His first documented session is a live date with vibraphonist Milt Jackson taped in Atlanta on July 4, 1980. Through 1981 he held the piano chair for a run of concerts at the Atlanta club e.j.'s that were later issued as a series of live albums: Harry "Sweets" Edison and Eddie "Lockjaw" Davis in February and November, trombonist Urbie Green on October 20 and 21, tenor saxophonist Scott Hamilton, and Clark Terry on December 18. Terry was the one who moved him. O'Neal followed the flugelhornist to New York City in 1981 and landed a regular job at the Blue Note, backing Dizzy Gillespie, Ray Brown, Nancy Wilson, Joe Pass and Kenny Burrell as they came through.

Art Blakey heard him there and hired him. O'Neal held the piano chair in the Jazz Messengers through 1982 and 1983, in the band with Terence Blanchard, Donald Harrison, Billy Pierce and Charles Fambrough, and the recorded trail runs right across both years: a live concert in Strasbourg on April 1, 1982, the studio album Oh-By the Way on May 20, 1982, a Nice festival set that July, the Aurex Jazz Festival in Japan in 1983 alongside Wynton Marsalis, Benny Golson and Curtis Fuller, and a Juan-les-Pins concert on July 18 of that year. Work with Blakey also meant accompanying singers, Sarah Vaughan and Carmen McRae among them. His debut as a leader, Coming Out, came out on Concord Jazz in 1983 with Ray Brown on bass, and in 1985 he made his Carnegie Hall debut as the solo opening act for Oscar Peterson.

Then it stopped. A mugging in 1986 drove him out of New York, and the next two decades were spent working in Atlanta, St. Louis, Montreal and back home in Detroit. The records from those years are scattered and mostly small: two Canadian trio albums with bassist Dave Young and drummer Terry Clarke on the Parkwood label, a private Michigan pressing called Reunion in 1989, On the Montreal Scene for Justin Time in 1996 with guitarist Russell Malone, and In Good Hands in 2002, cut in Ann Arbor with Peter Washington and Lewis Nash. He was diagnosed HIV positive in 1998, lost his health insurance as he grew too ill to work regularly, could not afford the medication, and dropped roughly a hundred pounds. One bright spot came in 2004, when on Oscar Peterson's recommendation he was cast as Art Tatum in the Ray Charles biopic Ray, playing "Yesterdays" in a nightclub scene.

He moved back to New York in 2010 with his health recovered and rebuilt a career from the bandstand up. A Sunday-night residency at Smalls in Greenwich Village and a late-Saturday slot at Smoke made him a fixture again, and SmallsLIVE documented a June 16, 2013 set as Live at Smalls. O'Neal Is Back, cut in Italy in November 2015 with bassist Luke Sellick and drummer Charles Goold, announced the return in its title. The record that carried furthest was In the Moment, made live in the studio at Sear Sound on May 9, 2017 for Smoke Sessions with Ben Rubens and Itay Morchi, and with Roy Hargrove and Grant Stewart guesting on named tracks. In February 2025 the Jazz Foundation of America and the Mellon Foundation named him to the inaugural class of twenty Jazz Legacies Fellows, an award carrying a $100,000 unrestricted grant. Everybody Loves Johnny O'Neal, a trio concert taped at Vancouver's Pyatt Hall on June 27, 2018, finally appeared on Cellar Music in April 2025.

O'Neal plays the mid-century virtuoso piano tradition without apology: Art Tatum's density and runs, Oscar Peterson's swing and two-handed authority, Barry Harris's bebop vocabulary. Harris, a fellow Detroiter, put the Tatum comparison plainly: "If ever somebody sounded like Art Tatum, it's him." What his colleagues single out is touch rather than speed. Mulgrew Miller is quoted in the 2006 concert film Tight naming the two most naturally talented musicians of his generation, both from Detroit, as Kenny Garrett and O'Neal, and describing O'Neal's touch as worth a million dollars. The second half of the act is the singing. He calls himself a piano player first who likes to shout the blues second, and his book runs well past the standards: Stevie Wonder's "Overjoyed," the Goffin and Masser ballad "Saving All My Love for You," Earth, Wind & Fire's "After the Love Has Gone" and the Stylistics' "People Make the World Go 'Round" all sit on In the Moment next to Duke Ellington and Henry Mancini. He writes too, sparingly: "Sweet Monk," "Churchill Grounds," "CGLS," "Being in Love with You" and "Tropical Breeze" are all his.