Little Steven grew up in the Jersey Shore music scene, and was an early friend and pre-E Street bandmate of Springsteen. In 1975 he was a member of the Dovells. He subsequently arranged the famous horn intro to Springsteen's Born to Run track Tenth Avenue Freeze-Out, and after that album he joined the E Street Band in the midst of their Born to Run tours. In those early years, Van Zandt supplied a large amount of the lead guitar work for the band in concert, as can be seen on the 1975 concert DVD within Born to Run 30th Anniversary Edition (later released as the CD Hammersmith Odeon London '75).

Van Zandt subsequently became a songwriter and producer for fellow Jersey shore act Southside Johnny and the Asbury Jukes in the mid- to late-1970s, penning their signature song I Don't Wanna Go Home, co-writing other songs for them with Springsteen, and producing their most-acclaimed record, Hearts of Stone. As such, Van Zandt became a key contributor to the Jersey Shore sound. Van Zandt then went on to share production credits on the classic Springsteen albums Darkness on the Edge of Town, The River, and Born in the U.S.A..

In 1999, Van Zandt took one of the core roles in The Sopranos, playing level-headed but deadly mob consigliere and strip club owner Silvio Dante. Van Zandt had no acting experience, and the unusual casting choice was made by series creator David Chase, who had remembered him as having an "interesting look" on Springsteen album photos.