John Lee Clayton Jr. was born August 20, 1952, in Venice, California, and started on bass in elementary school, moving through strings class, junior orchestra, and high school jazz band and orchestra before picking up soul and R&B gigs around Los Angeles as a teenager. In 1969, at sixteen, he enrolled in bassist Ray Brown's jazz class at UCLA, whose own career is covered in full in his JazzProfiles.com profile. Brown had Clayton drill every major, minor, whole-tone, and diminished scale alongside every chord type, and pushed him to learn as many jazz and popular standards as he could hold — a rigorous grounding that began a mentorship lasting more than three decades and that Clayton has repeatedly called the most influential education of his career. At nineteen, while still a student, Clayton landed a seat as house bassist on Henry Mancini's television series The Mancini Generation (1972). He completed a Bachelor of Music in double bass at Indiana University in 1975.

After graduating, Clayton toured with the Monty Alexander Trio (1975-1977) — a lineup that also featured a young drummer named Jeff Hamilton, whose own career is covered in full in his JazzProfiles.com profile, and that was captured live at the 1976 Montreux Jazz Festival on the album Montreux Alexander. Clayton then spent two years with the Count Basie Orchestra (1977-1979) before accepting the principal bass chair with the Amsterdam Philharmonic Orchestra in the Netherlands, a position he held for five years (1980-1985). His son, pianist Gerald Clayton, was born in Utrecht during that stretch. In between, back in Los Angeles in 1977, Clayton and his brother, alto saxophonist Jeff Clayton, formed the Clayton Brothers, releasing their debut album, Jeff & John, on Concord Jazz in 1979; the group went dormant while John was overseas.

Clayton returned to Los Angeles from Amsterdam in 1985 and, with Jeff Hamilton and Jeff Clayton, co-founded the Clayton-Hamilton Jazz Orchestra (CHJO), a Los Angeles big band built to play Clayton's own arrangements with the discipline of the classic Basie book and the drive of a working road band; the same year, he also revived the Clayton Brothers as an active group. DownBeat and JazzTimes have each named the CHJO Best Big Band in America, and its catalog runs from Groove Shop and Heart and Soul in its earliest years through Charles Aznavour & The Clayton-Hamilton Jazz Orchestra (2009) to 2023's And So It Goes, dedicated to Jeff Clayton's memory after his death in 2020 and nominated for the Best Large Jazz Ensemble Album Grammy at the 2025 ceremony. John and Jeff Clayton are the father and uncle, respectively, of pianist Gerald Clayton, who has performed and recorded with the Clayton Brothers Quintet since the early 2000s. In 2006, the Los Angeles Jazz Society named John Clayton and Jeff Hamilton its Musicians of the Year together.

Alongside his bandleading, Clayton built one of the busiest arranging careers in mainstream jazz. He served as big-band arranger and conductor on Dee Dee Bridgewater's Dear Ella (1997, Verve), whose own career is covered in full in her JazzProfiles.com profile, a tribute to Ella Fitzgerald that won the 1998 Grammy for Best Jazz Vocal Album. In 1991 he arranged the orchestral backing for Whitney Houston's rendition of "The Star-Spangled Banner" at Super Bowl XXV, a recording that was later certified platinum. He won his own Grammy in 2008, for Best Instrumental Arrangement Accompanying Vocalist(s), for "I'm Gonna Live Till I Die" on Queen Latifah's Trav'lin' Light (2007), and has picked up roughly ten further nominations across his career, including for the Clayton Brothers' Brother to Brother (2008) and the CHJO's And So It Goes. His arranging and performing clients span Diana Krall, Natalie Cole, Milt Jackson, Nancy Wilson, Quincy Jones, George Benson, Dr. John, Gladys Knight, Regina Carter, McCoy Tyner, and Charles Aznavour; he also played bass on Paul McCartney's Kisses on the Bottom (2012) and arranged for Yo-Yo Ma. Away from arranging, he has continued to record as a bassist in his own right, most visibly alongside Ray Brown and Christian McBride on the SuperBass summit albums (1997 and 2001) and, more recently, under his own name on Family Tree (2023, featuring Houston Person) and John Clayton & Mulgrew Miller Play Duets: Talk to Me About Mulgrew (2024).

Clayton has also built a substantial career as an educator and administrator: 21 years on the faculty of the USC Thornton School of Music, past president of the International Society of Bassists, a five-year term as president of the American Society of Music Arrangers and Composers, founder of the Vail Jazz Workshop, two decades directing the jazz program at Centrum's Port Townsend Jazz Camp, artistic director of the Lionel Hampton International Jazz Festival, and Artistic Director of Jazz for the Los Angeles Philharmonic's Hollywood Bowl series from 1999 to 2001.

Clayton's playing and writing carry the direct stamp of his three-decade mentorship under Ray Brown — a big, centered tone and rock-steady time that anchors everything he leads — combined with an arranger's ear trained across genres from Basie-style big band to pop orchestration. That combination made him equally credible leading the Clayton-Hamilton Jazz Orchestra's disciplined, riff-driven book, playing acoustic bass summits with Brown and Christian McBride, and writing charts for singers as different as Diana Krall, Whitney Houston, and Queen Latifah. His Grammy-winning arrangement work shows the same instinct that runs through his bass playing: economical, harmonically sophisticated, and built to serve the artist in front of the band rather than the arranger behind it.