Slick got his start in the club scene of his hometown, New York City, where he quickly gained a reputation as a unique and talented guitarist. In 1974, friend and film composer Michael Kamen recommend Slick to David Bowie as Mick Ronson's replacement on the Diamond Dogs tour.

Although Bowie supplied most of the guitar work on Diamond Dogs, Slick managed to duplicate and expand on the tracks while injecting his own style into the live show, resulting in one of the greatest live rock guitar albums of all time, David Live, recorded at the Tower Theater in Philadelphia in 1974.

Slick remained with Bowie for his next two studio albums, which saw the singer transform into his “Thin White Duke” persona, resulting in the classic Young Americans (1975) and the more experimental Station to Station (1976). It was around this time that Slick met John Lennon, who would ask Slick to join him in the studio a few years later on what would turn out to be Lennon's final studio album, Double Fantasy.
During this time, Slick also launched his solo career, resulting in the records Razor Sharp (1976) and Earl Slick Band (1976)
In the following years, Slick would continue to record and tour with some of the world's most influential artists.
In 2000, Slick accepted an offer to rejoin Bowie full-time, touring steadily and appearing on Bowie’s 2002 studio effort, Heathen, and 2003’sReality. “Earl is a legendary guitar star and a musician of great feeling,” says Bowie. “His playing is earthy, timeless and never less than stellar.” In 2003, Bowie, Joe Elliott (Def Leppard), Robert Smith (The Cure), and other notables joined Slick for his solo release, Zig Zag.