Weldon Jonathan Irvine Jr. was born in Hampton, Virginia, on October 27, 1943. His grandparents raised him on the campus of Hampton Institute, where his grandfather was dean of the men's college and his grandmother played upright bass in regional classical groups. He graduated from George P. Phenix High School in 1961, started on piano as a teenager, and studied literature at Hampton, although music had become his first love once he discovered jazz. In 1965 he moved to New York City and settled in the St. Albans section of Queens, which remained his home base for the rest of his life.

In New York he went to work for Nina Simone as her organist, arranger, bandleader and road manager. Simone first sang "To Be Young, Gifted and Black" to a crowd of about 50,000 at the Harlem Cultural Festival on August 17, 1969, and recorded it two months later at New York's Philharmonic Hall, in the concert released in January 1970 as Black Gold. Irvine wrote the lyrics and played organ on that album. The title came from Lorraine Hansberry's autobiographical play, and the song was written in memory of Hansberry, who died in 1965 at the age of 34. Issued as a single, it reached No. 8 on the R&B chart and No. 76 on the Hot 100 in January 1970, and it is widely regarded as an anthem of the Black pride movement. His own jazz credits begin in the same period. He plays tambourine on Freddie Hubbard's Straight Life, recorded on November 16, 1970 with Herbie Hancock, George Benson, Ron Carter, Jack DeJohnette and Joe Henderson, and the album includes Hubbard's thirteen-minute performance of Irvine's composition "Mr. Clean."

His own records began on a label he ran himself. Liberated Brother (Nodlew Music, 1972) was produced by Irvine, who plays piano, RMI electric piano, Moog synthesizer and melodica on it, with Napoleon Revels and Chip Lyles on drums and percussion, Tommy Smith on guitar and James Stroud on tenor saxophone. It carries his own first recording of "Mr. Clean." Time Capsule (Nodlew Music, 1973) followed, and in 1974 he released In Harmony on the Strata-East label. He also wrote for the stage: Wikipedia calls him a playwright, and his musical Young, Gifted and Broke played the Billie Holiday Theatre in Brooklyn, the start of a long association with that theater.

RCA signed him in 1974. Cosmic Vortex (Justice Divine), recorded at RCA's Studio D in New York with Irvine producing, arranging and conducting, was a large-scale record built around his lyrics and vocals, with Cornell Dupree on guitar, Bob Cranshaw on bass, Lenny White among four drummers and Jimmy Owens among three trumpeters. Spirit Man (1975) dropped the vocals and put the keyboards and electronics in front, with Sonny Fortune on alto saxophone. Its opening track, "We Gettin' Down," was later sampled by A Tribe Called Quest on "Award Tour" from Midnight Marauders (1993). Sinbad (1976), his third RCA album, brought in Don Blackman on piano and lead vocals, Eric Gale, Steve Gadd, Michael Brecker and Randy Brecker, and covered Stevie Wonder's "Don't You Worry 'Bout a Thing" and Marvin Gaye's "What's Goin' On." A profile compiled by his high school's alumni project says he also led a seventeen-piece group in which, at various times, Billy Cobham, Randy Brecker, Bennie Maupin and Don Blackman played. His leader albums became sparse after the 1970s: The Sisters (1979), then Weldon & The Kats (Nodlew Music, 1989).

The records returned to circulation through hip-hop and the rare-groove scene. In Harmony and Weldon & The Kats were reissued by Luv N' Haight in 1992, and Music Is the Key, a 1994 collection on that label, introduced him to a new audience. He mentored many New York hip-hop artists, among them Q-Tip and Mos Def. He played keys on "Astronomy (8th Light)" on Black Star's Mos Def & Talib Kweli Are Black Star (1998) and contributed to Mos Def's Black on Both Sides (1999). His last major project was The Amadou Project: The Price of Freedom (1999), an album of new songs by hip-hop, jazz, funk and R&B artists made in response to the police shooting of Amadou Diallo. In 2000 he sang the vocal introductions and played Fender Rhodes on parts of Late Night Blues, the album by the British drum and bass producer Big Bud.

Irvine took his own life on April 9, 2002, in Uniondale, New York, at the age of 58. A memorial concert on January 18, 2003 at The Bottom Line in Manhattan, produced by the Black Spectrum Theatre of Jamaica, Queens, brought together Marcus Miller, Don Blackman, Lenny White and other musicians who had worked with him or learned from him. Madlib, Mr. Dibbs and Breakestra recorded "Suite for Weldon" in 2003, and Madlib released the full-length A Tribute to Brother Weldon in 2004. The documentary Digging for Weldon Irvine, directed by Victorious De Costa, appeared in 2019. In 2023 the Japanese company P-Vine acquired the master recordings and copyrights held by his estate, including "To Be Young, Gifted and Black," and has since issued new vinyl singles and a compilation from the catalog.

Irvine wrote and played where jazz harmony, funk grooves and gospel feeling meet. His keyboard work is electric from the early 1970s, with RMI electric piano, Moog and other synthesizers, and AllMusic hears the instrumental Spirit Man as running parallel to Herbie Hancock's fusion records in imagination and force. The same reviewer describes Cosmic Vortex as a record that explores spiritual and political ground on the scale major-label money allows, with an unusual emphasis on lyrics and vocals, and describes Sinbad as inspired by the soul-searching records of Marvin Gaye and Stevie Wonder. The Discogs artist profile places him among the contributors to the 1970s Black Arts Movement, and credits him with more than 500 songs and a large body of stage plays.

His standing is different on each side of the line this profile sits on. On the jazz side he is a keyboardist and composer with real credits, among them Freddie Hubbard's Straight Life and the "Mr. Clean" that Hubbard recorded. On the pop and soul side he is the lyricist of a chart single that became a civil rights anthem, and a soul and funk bandleader described as an artist of moderate success but large influence. The largest part of his reputation came afterward, from hip-hop producers who sampled his records, from the rare-groove and acid jazz collectors who reissued them, and from the younger musicians he taught and advised in Queens. Sony Music Japan's biography notes that his records are more popular with club listeners and DJs than with jazz audiences, while Black jazz listeners and hip-hop artists continue to respect him.