Gene Harris was born Eugene Haire on September 1, 1933, in Benton Harbor, Michigan. He taught himself piano, was playing popular songs by ear by the age of nine, and listened closely to the local bandleader Charles Metcalf and the boogie-woogie pianists Pete Johnson and Albert Ammons. He entered the U.S. Army in 1951 and played in Army bands, among them the 82nd Airborne Division Band, and after his discharge in 1954 he toured with several bandleaders.

In 1956 he formed a group in Benton Harbor called the Four Sounds, with bassist Andrew Simpkins, drummer Bill Dowdy, and a saxophonist, Lonnie Walker, who left within a year, which left the piano trio that became The Three Sounds. The trio worked Michigan and the Washington, D.C., area before moving to New York in 1958. It backed Nat Adderley on Branching Out for Riverside that year, then signed an exclusive contract with Blue Note, whose first Three Sounds album, Introducing the Three Sounds, was recorded at Rudy Van Gelder's studio in Hackensack, New Jersey, on September 16 and 18, 1958, and issued that December. Nine Blue Note albums followed between 1958 and 1962, among them LD+3 with Lou Donaldson (recorded February 18, 1959) and Blue Hour with Stanley Turrentine (recorded in 1960, released in March 1961), and the group toured the country's jazz clubs steadily.

After 1962 the trio moved among labels. It made Blue Genes and, with producer Creed Taylor, Anita O'Day & the Three Sounds (recorded October 12 to 15, 1962) for Verve, working with Anita O'Day; then three albums for Mercury, including Live at the Living Room (1964); then Three Moods and Beautiful Friendship (both 1965) for Limelight, the latter with horns and strings arranged by Julian Lee. Blue Note brought the group back in 1966 for Vibrations, Live at the Lighthouse, Coldwater Flat with an orchestra led by Oliver Nelson, and the Monk Higgins-arranged Elegant Soul (recorded September 19 and 20, 1968) and Soul Symphony (1969). The personnel turned over in those years: Kalil Madi and then Donald Bailey replaced Dowdy in the mid-1960s, and Simpkins's last album with the group was Elegant Soul. The group's name survived into the early 1970s, and Harris went on recording for Blue Note under his own name with a lighter, electric and jazz-funk touch: The 3 Sounds (1971), Gene Harris of the Three Sounds (1972, with bassist Ron Carter and guitarist Cornell Dupree), Yesterday, Today & Tomorrow (1973), Astral Signal (1974), Nexus (1975), In a Special Way (1976), and Tone Tantrum (1977).

In the late 1970s Harris moved to Boise, Idaho, and largely stepped back from touring, though he kept playing regularly at the Idanha Hotel. Bassist Ray Brown persuaded him to return to the road in the early 1980s. Harris recorded Live at Otter Crest (1981) and Hot Lips (1982) for small labels, then joined the Ray Brown Trio, whose first album with him, Soular Energy (recorded 1984, Concord, 1985), began a run of Concord albums that includes Don't Forget the Blues, Bam Bam Bam (1989), Summer Wind: Live at the Loa, and Moore Makes 4; he stayed with Brown into the early 1990s. He also played on Milt Jackson's Soul Route for Pablo, Benny Carter's A Gentleman and His Music (1985), and B.B. King's Live at the Apollo (1991), billed as featuring Harris and the Philip Morris Superband. As a leader he recorded The Gene Harris Trio Plus One (1986) for Concord, a live set from New York's Blue Note with Brown, drummer Mickey Roker, and Turrentine as guest.

Brown and the producer Bennett Rubin then proposed a Count Basie tribute with Harris as leader, and the Gene Harris All Star Big Band recorded Tribute to Count Basie in March and June 1987 at Evergreen Studios in Burbank, California, with arrangements by Frank Wess and players including Herb Ellis, Plas Johnson, and Jeff Hamilton. Concord released it in 1988, and it received a Grammy nomination at the 1989 ceremony. The band grew into the Philip Morris Superband, a touring big band sponsored by Philip Morris, with Harris at the piano and a lineup that included Harry "Sweets" Edison, James Moody, Brown, Wess, Ellis, Hamilton, Gary Smulyan, and Michael Philip Mossman. A tour planned as 31 concerts in 24 cities on five continents opened at New York's Town Hall in September 1989, and the band recorded Live at Town Hall, N.Y.C. there on September 23, 1989, followed by World Tour 1990.

Alongside the big band Harris led a Concord quartet, usually with guitarist Ron Eschété, bassist Luther Hughes, and drummer Harold Jones or Paul Humphrey. Its albums include Listen Here! (1989), Black and Blue (1991), Like a Lover (1992), Brotherhood (recorded 1992), A Little Piece of Heaven, Funky Gene's, and It's the Real Soul (recorded 1995), the last with Wess on tenor saxophone and flute. He made At Last (1990) with Scott Hamilton as co-leader, the solo recital Gene Harris at Maybeck, recorded at Maybeck Recital Hall in Berkeley in August 1992, and in 1997 the albums In His Hands and (Down Home) Blues with organist Jack McDuff, with his daughter Niki Haris as a guest singer. In May 1996 he recorded a quartet engagement in London with guitarist Jim Mullen, bassist Andrew Cleyndert, and drummer Martin Drew; Resonance Records issued it as Live in London (2008) and Another Night in London (2010).

In 1996 Harris helped set up the Gene Harris Endowment, which funds jazz scholarships at Boise State University, and in 1998 he helped launch the Gene Harris Jazz Festival there. His last album, Alley Cats, was recorded live at Dimitriou's Jazz Alley in Seattle in December 1998 and released by Concord in October 1999. He passed away in Boise on January 16, 2000, at the age of 66, from kidney failure while waiting for a transplant. His survivors included his wife, daughters Beth and Niki Haris (a singer), and a son, Gene Harris Jr. A bandshell in Boise's Ann Morrison Park carries his name, and Boise State's Gene Harris Jazz program, rooted in that 1998 festival, continues to run masterclasses, workshops, and student ensembles in his memory.

Harris played a warm, blues- and gospel-rooted piano in the soul-jazz mold, a trio style that writers trace to Ahmad Jamal, with Erroll Garner and Oscar Peterson as the other strong influences on his touch and drive. He was admired for technical precision, a personal sound, and unexpected chord substitutions, and he was at his best in the leisurely blues, ballads, and standards that fill the Three Sounds albums. AllMusic's review of the debut, Introducing the Three Sounds, observed that the trio's sound was fully formed from the start and never changed much afterward, and The Penguin Guide to Jazz described his Maybeck recital as typically straight-ahead and without frills. In the Blue Note years he also pushed the group toward funk and orchestral pop-soul, as on Elegant Soul and Soul Symphony, and a sample from "Put On Train" on his 1971 album became the backing for the Beastie Boys' 1989 song "What Comes Around." Pianists elsewhere have named him as a model: the Korean pianist Ki Moon Sung was nicknamed "Korea's Gene Harris," and the Italian-born pianist Francesca Tandoi counts him among her early influences.