Wynton Learson Marsalis was born October 18, 1961, in New Orleans, Louisiana, the second of six sons of pianist and educator Ellis Marsalis Jr. and Dolores Ferdinand Marsalis. He received his first trumpet at age six as a gift from bandleader Al Hirt, though serious practice did not begin until he was twelve. He studied classical trumpet at Benjamin Franklin High School and the New Orleans Center for Creative Arts while absorbing jazz informally at home, and at fourteen he won a citywide music contest performing a Haydn trumpet concerto with the New Orleans Philharmonic. At seventeen he was admitted to the Tanglewood Music Center, and in 1979 he enrolled at the Juilliard School in New York to study classical trumpet performance, leaving in 1981 without completing the degree once professional work took over.

That professional work began immediately: in 1980 Marsalis toured Europe with Art Blakey and joined the Jazz Messengers outright, remaining until 1982 and appearing on the band's Album of the Year (1981, Timeless), part of the early-1980s "young lions" wave that also included his older brother Branford Marsalis. In 1982 he signed to Columbia Records, released his self-titled debut album, and formed his own quintet with Branford on saxophones, Kenny Kirkland on piano, Charnett Moffett on bass, and Jeff "Tain" Watts on drums. The group's Think of One (1983) and Hot House Flowers (1984) built his reputation quickly, and in 1983 he became the first musician to win Grammy Awards in both jazz and classical categories in the same year, at age twenty-two; he repeated the feat in 1984. Black Codes (From the Underground) (1985), recorded with Branford, Kirkland, Watts and bassist Ron Carter, is widely regarded as the quintet's creative peak and won two more Grammys.

When Branford and Kirkland left in the mid-1980s to tour with Sting, Marsalis re-formed his band around pianist Marcus Roberts, bassist Robert Hurst and Watts, documenting the new quartet on J Mood (1986) and Marsalis Standard Time, Vol. 1 (1987), both Grammy winners. The band expanded through the late 1980s and early 1990s into a septet featuring Wessell Anderson, Todd Williams, Wycliffe Gordon, Eric Reed, Reginald Veal and Herlin Riley, recording extended, suite-length compositions including The Majesty of the Blues (1989), the ballet score Citi Movement (Griot New York) (1993), and the gospel-inflected In This House, On This Morning (1994).

Marsalis had helped establish a "Classical Jazz" summer concert series at Lincoln Center in 1987; it grew into a full department and, in 1996, an independent constituent of Lincoln Center in its own right, with Marsalis as founding artistic director of the Jazz at Lincoln Center Orchestra, a post he still holds. In 1997 his oratorio Blood on the Fields, a two-and-a-half-hour work for the orchestra tracing the journey of two enslaved people to freedom, made him the first jazz musician to win the Pulitzer Prize for Music. Alongside performing and composing, he became a prominent jazz educator: his PBS series "Marsalis on Music" and NPR's "Making the Music" both won George Foster Peabody Awards in the mid-1990s, and he later directed the Juilliard Jazz Studies program and was named cultural correspondent for CBS This Morning in 2011.

His later career has mixed large-scale composition with genre-crossing collaboration. All Rise (2002), a symphonic work for the New York Philharmonic and Jazz at Lincoln Center Orchestra under Kurt Masur (recorded with Esa-Pekka Salonen conducting), and Congo Square (2008), co-led with Ghanaian percussionist Yacub Addy and his ensemble Odadaa!, extended his interest in large ensembles beyond straight jazz instrumentation. He recorded Two Men with the Blues (2008) with country singer Willie Nelson, produced by his brother Delfeayo Marsalis, and Play the Blues: Live from Jazz at Lincoln Center (2011) with guitarist Eric Clapton. His sacred choral work The Abyssinian Mass (2016) marked the 200th anniversary of Harlem's Abyssinian Baptist Church, and in 2019 he wrote a Violin Concerto and Fiddle Dance Suite for classical violinist Nicola Benedetti, whom he married in 2024. He was named an NEA Jazz Master in 2011 and inducted into the DownBeat Hall of Fame in 2017, and in January 2026 Jazz at Lincoln Center announced he will step down as artistic director in July 2027 after three decades in the role, continuing afterward as an advisor and occasional performer. He has won nine Grammy Awards across jazz and classical categories and holds honorary degrees from more than a dozen universities.

Marsalis is the most visible standard-bearer of what he and others call "straight-ahead" jazz: acoustic instrumentation, blues feeling, swing rhythm, and a lineage running from New Orleans jazz and Duke Ellington through bebop, which he has argued should anchor the music against the electric fusion and free-jazz directions of the 1970s. His own cited influences include Ellington, Miles Davis, Clark Terry, Dizzy Gillespie, Charlie Parker, Thelonious Monk and Clifford Brown, and his technically immaculate, historically referential trumpet style has in turn shaped a generation of conservatory-trained jazz musicians who came up through Jazz at Lincoln Center's programs. His traditionalism has also drawn sustained criticism: pianist Keith Jarrett said in 1997 that his playing "sounds like a high school trumpet player," and Marsalis's own public dismissals of Miles Davis's fusion era, of hip-hop, and of the post-1965 avant-garde have made him as much a lightning rod for jazz's internal culture wars as a virtuoso performer.