Nathaniel Carlyle Adderley was born November 25, 1931, in Tampa, Florida, the younger brother of alto saxophonist Julian "Cannonball" Adderley. Their father played trumpet professionally and passed the instrument down through the family, first to Cannonball and then to Nat. The family later moved to Tallahassee, where both brothers attended Florida A&M University and, as teenagers, played alongside a young Ray Charles in the local music scene. Nat started on trumpet in 1946 and switched permanently to cornet around 1950, drawn to the instrument's darker, more conical tone over the trumpet's brighter cylindrical sound; that dark, earthy cornet tone became his signature. He served in the U.S. Army from 1951 to 1953, playing in an Army band under his brother's direction and touring Korea, then returned to civilian music, working with trombonist J.J. Johnson and briefly with Woody Herman's band.

A 1955 sit-in at Café Bohemia in Greenwich Village, where Cannonball substituted for saxophonist Jerome Richardson, launched both brothers' New York careers almost overnight. That same year Nat cut his first date as a leader, Introducing Nat Adderley (recorded September 6, 1955, for Wing/EmArcy), featuring Cannonball, Horace Silver, Paul Chambers, and Roy Haynes. The brothers formed the first Cannonball Adderley Quintet in 1956, but it disbanded within a year for lack of commercial interest; Nat spent the interim freelancing, including a February 19, 1958 sideman date on Tommy Flanagan's piano chair for J.J. Johnson's J. J. in Person! (Columbia) and a 1959 session with Woody Herman's band, released as The Fourth Herd, alongside Zoot Sims.

The Adderleys reunited their quintet in 1959, and it quickly became one of the era's most commercially successful jazz groups, breaking through with Bobby Timmons's "This Here." Nat served as the group's cornetist, a key composer, and its road manager for the remainder of its run. In January 1960 he wrote "Work Song," inspired by a boyhood memory of hearing convict laborers sing on a Florida chain gang; he first recorded it, as a 16-bar minor blues, on his own Riverside album Work Song (recorded January 25 and 27, 1960, at Reeves Sound Studios, New York), built around an unusual frontline of cornet, Wes Montgomery's guitar, and Sam Jones's cello, with Bobby Timmons, Percy Heath, Keter Betts, and Louis Hayes rounding out the sessions. Days later, on February 1, 1960, the Cannonball Adderley Quintet cut its own version for Them Dirty Blues (Riverside, with pianists Barry Harris and Bobby Timmons, Sam Jones, and Louis Hayes), pairing it with Timmons's "Dat Dere." Oscar Brown Jr. added lyrics in 1961 for his album Sin & Soul, and "Work Song" became a jazz standard and a steady earner Nat later called his "Social Security song."

Through the 1960s Nat kept up a busy parallel career as a leader alongside the Quintet's own hit run (including "Mercy, Mercy, Mercy" in 1966, written by the group's pianist Joe Zawinul). His Riverside date That's Right! (1960) placed his cornet in front of a five-saxophone "Big Sax Section" including Yusef Lateef, Jimmy Heath, and Charlie Rouse. Naturally! (1961, Jazzland) split its two sessions between a group with Joe Zawinul, Sam Jones, and Louis Hayes, and one with Wynton Kelly, Paul Chambers, and Philly Joe Jones. Autobiography (recorded December 1964 to January 1965, Atlantic) again featured Zawinul on piano in a larger horn ensemble. Nat also ghost-played cornet for Sammy Davis Jr.'s trumpet-playing character in the 1966 film A Man Called Adam. By the late 1960s he moved toward a more commercial, funk-inflected sound on A&M releases You, Baby (1968) and Calling Out Loud (1969, produced by Creed Taylor for CTI).

Cannonball's sudden death in August 1975, four weeks after a stroke, ended the Quintet and interrupted a musical the brothers had been co-writing, Shout Up a Morning, based on the John Henry folk legend; Nat completed it, and it was staged nationally in 1986. He spent his remaining 25 years as a headlining leader, touring Europe and Japan, teaching briefly at Harvard, and forming a new quintet with bassist Walter Booker, drummer Jimmy Cobb, and, later, altoist Vincent Herring, as well as a larger touring group billed as the Adderley Brotherhood in 1980. He formed the Paris Reunion Band in the 1990s and led the Riverside Reunion Band at the 1993 Monterey Jazz Festival and on a 1994 European tour. In 1997 he joined the faculty of Florida Southern College in Lakeland as artist-in-residence, founded what became the school's long-running Child of the Sun Jazz Festival, and was inducted into the Jazz Hall of Fame in Kansas City. His playing range had narrowed by the late 1960s, but he kept performing into his final year. Nat Adderley died January 2, 2000, in Lakeland, Florida, of complications from diabetes, at age 68, and was buried at Southside Cemetery in Tallahassee near his brother.

Adderley built his identity around the cornet at a time when the trumpet dominated jazz brass, prizing its darker, more compact sound and its historical link to the earliest jazz cornetists; he was also unafraid to dip below the instrument's typical range for brief, guttural effects before snapping back to the normal register. Alongside his brother and pianist Bobby Timmons, he was a principal architect of soul jazz, a style built on simple, gospel-inflected harmony, a heavy blues feel, and catchy, riff-based themes, most fully realized in his own composition "Work Song." Roughly half his recorded output leaned toward straight hard bop rather than soul jazz. AllMusic's Scott Yanow, reviewing the Work Song album, called him "heard throughout in peak form, playing quite lyrically," and The Penguin Guide to Jazz praised the same record as "laced with a funky blues feel."