John Harle's first instrument was the clarinet, and his teacher on that instrument was Jack Brymer. At age 13, Harle expressed to Brymer the frustration he was experiencing in trying to create the clarinet sound he wanted. Brymer suggested a switch to the saxophone, which proved a natural fit for Harle. His skills soon won him admission into the Royal College of Music in London, where he studied until 1980; he supplemented his education with two years at the Paris Conservatoire. Back in London, Harle made the acquaintance of composer Michael Nyman, joining the latter's band in 1982; Nyman eventually supplied Harle with a full-scale concerto, entitled Where the Bee Dances. Through his work with Nyman, Harle also gained entry into the world of film and television scores. In 1987, Harle was named professor of Saxophone and Chamber Music at the Guildhall School of Music and Drama in London. In 1988 he was the subject of a BBC2 special, "A Man and his Sax"; that same year, the score he co-wrote with Stanley Myers for the film Prick Up Your Ears won the Best Achievement in a Feature Film award at Cannes.
By 1991, Harle was recording for both EMI and Argo as a saxophone soloist. Harle's work for EMI reflected his standard concert programs. These included the Debussy Rhapsodie, Villa Lobos' Fantasia and In the Shadow of the Duke, Harle's tribute to his idol, Duke Ellington saxophonist Johnny Hodges. Harle's Argo recordings feature works written by living composers, including Dominic Muldowney, Gavin Bryars, Luciano Berio, and Mike Westbrook, with Harle specifically in mind. In 1993, Harle composed a commercial jingle for Nissan entitled Nissan Donna; Jazzy B of the hip-hop group Soul II Soul remixed the tune as a single, which made it to number six on the British pop charts. Harle's performance of Harrison Birtwistle's Panic at the Last Night of the Proms in 1995 garnered him a great deal of positive critical attention. Since then, Harle has concentrated strongly on serious composition in addition to his saxophone playing, concertizing, and film work. In 1996 he collaborated with vocalists Sarah Leonard and Elvis Costello on the album Terror and Magnificence, released on Argo. The disc went into the top ten in the U.K., and was followed by a brief concert tour the following year. The following year, Harle contributed to another hit record as part of the arranging staff that worked on Sir Paul McCartney's Standing Stone. The year 1998 witnessed the debut of Harle's opera Angel Magick, based on the life of sixteenth century alchemist John Dee, with a libretto by David Pourtnoy. Angel Magick gained some notoriety for its introduction of full frontal nudity to the stage of the Proms.
As a soloist, Harle has toured worldwide, and claims to be the most recorded classical saxophonist in history. In 2000, Harle renewed his association with Sir Paul McCartney, arranging McCartney's Nova, a tribute to the ex-Beatle's late wife, for the memorial benefit album A Garland for Linda.