Steven Van Zandt was born on November 22, 1950, in Boston, Massachusetts. He was born as Steven Lento and is of Southern Italian descent (his grandfather was from Calabria and his grandmother's parents were Neapolitans). He lived at 16 Edgecliff Road in Watertown, Massachusetts.

His mother, Mary Lento, remarried in 1957 and he took the last name of his stepfather, william Brewster Van Zandt. The family moved from Massachusetts to Middletown Township, New Jersey, when he was seven.

Van Zandt found his love for music at an early age, when he learned how to play the guitar. He watched the performances of the Beatles on the Ed Sullivan Show and Rolling Stones on Hollywood Palace in 1964 and referred to the former as "The Big Bang of Rock n' Roll". He said that when he was 13, George Harrison was his favorite Beatle, but he is now friends with Paul McCartney and Ringo Starr. Around August 1964, he formed his first band, the Whirlwinds, which was short lived. He later formed the Mates in 1965 and joined the Shadows in May 1966. Van Zandt has cited British Invasion bands such as the Dave Clark Five, as well as Ravi Shankar and the culture of India as early influences.

Van Zandt grew up in the Jersey Shore music scene, and was an early friend and pre-E Street bandmate of Bruce Springsteen. Springsteen met Van Zandt for the first time in 1966 or 1967 when Springsteen went to the Hullabaloo club in Middletown. Van Zandt was performing a cover of the Turtles' "Happy Together" with the Shadows. They performed together in bands such as Steel Mill and the Bruce Springsteen Band. During the early 1970s, Van Zandt worked in road construction for two years, before returning to show Business. In 1973, he toured with The Dovells. The tour ended in Miami during Dick Clark's New Year's Show at the Deauville Hotel. After going back to Jersey, Van Zandt continued to wear Hawaiian shirts because he did not like winter, which was how he got the nickname "Miami Steve".

Van Zandt attended Middletown High School, where he got kicked out for having long hair. He went back to school to make his mother happy and graduated in 1968.

Van Zandt became a Songwriter and Producer for fellow Jersey shore act Southside Johnny and the Asbury Jukes in 1974, penning their signature song "I Don't Want to 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. He also produced two Gary U.S. Bonds' albums. Van Zandt then went on to share production credits on the classic Springsteen albums The River and Born in the U.S.A. The first Springsteen song he co-produced was "Hungry Heart." In 1989, Jackson Browne covered the 1983 Van Zandt composition "I Am A Patriot" on his World in Motion album. Van Zandt has produced a number of other records, including an uncredited effort on the Iron City Houserockers' Have A Good Time (But Get Out Alive). Less successful was his work on Lone Justice's second album Shelter, which was a career-ending flop for the Los Angeles cowpunk band.

In those early years, Van Zandt supplied a great deal 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). In 1984, Van Zandt left the E Street Band. He originally joined to see Bruce Springsteen rise in success, and once the band rose to that success he left. Despite leaving the band, he appeared as a special guest at certain concerts on the Born in the U.S.A. Tour and appeared in a couple of videos, including the one for Glory Days.

Van Zandt is married to Actress Maureen Van Zandt (formerly Maureen Santoro), who portrayed his wife Gabriella Dante in the TV series The Sopranos. They married in New York City on December 31, 1982. Bruce Springsteen was the best man at the ceremony, which was presided over by Reverend Richard Penniman (Little Richard). Singer Percy Sledge sang his classic "When a Man Loves a Woman" at the reception.

After leaving the E Street Band in 1984, Van Zandt used his Celebrity as a musician to fight issues surrounding apartheid in South Africa by creating a group called the Artists United Against Apartheid.

This Activist group was created in 1985 by Van Zandt and record Producer Arthur Baker. Van Zandt and Baker assembled over 54 different artists to record an album entitled Sun City in order to raise awareness about the apartheid policy in South Africa. The title referred to a resort in South Africa that catered to wealthy white tourists. The resort upheld racist apartheid policies, yet many famous entertainers chose to perform there. Artists that took part in the making of the album included Bruce Springsteen, Peter Gabriel, Miles Davis, Bob Dylan and Lou Reed.

In 1987, he released the album Freedom - No Compromise, which continued the political messaging. Some U.S. appearances in that year as opening act for U2's arena-and-stadium Joshua Tree Tour continued in the same vein, but were not well received by some audiences. Both the record and his concerts were popular in Europe. He also performed at the "Nelson Mandela 70th Birthday Tribute" concert at Wembley Stadium in 1988.

His fourth album, 1989's Revolution, attracted little attention. In 1995, Van Zandt wrote, produced, and sang "The Time of Your Life" for the Soundtrack to the film Nine Months. He also toured with Bon Jovi during the first European leg of their These Days Tour. Due to a loss of recording contract, his next album, Born Again Savage, was not released until 1999. Since then, Van Zandt has recorded another album, Nobody Loves and Leaves Alive with his garage band the Lost Boys. Although the album remains unreleased, three tracks from it were heard on the Sopranos television show: "Nobody Loves and Leaves Alive", "Affection", and "Come for Me". "Affection" appeared on The Sopranos: Peppers & Eggs (Music From the HBO Original Series).

In 1994, Van Zandt produced the eponymous debut album of the punk rock band Demolition 23 which featured ex-Hanoi Rocks members Michael Monroe and Sami Yaffa. Van Zandt also co-wrote six songs for the album with Monroe and Jude Wilder. In 1995, Van Zandt aided Meat Loaf with the song "Amnesty Is Granted" off of his Welcome to the Neighborhood album. In 2004, he contributed the song "Baby Please Don't Go" to Nancy Sinatra's self-titled album.

Later in life, Van Zandt returned to the E Street Band when it was reformed (briefly in 1995, and on an ongoing basis since 1999) and remains with it. By now, his guitar playing had mostly been reduced to a background rhythm role, due to Nils Lofgren's position in the band and his capability as a lead Guitarist. In addition, Springsteen had begun taking many more of guitar solos as his music became more guitar-centered. Van Zandt said on the Howard Stern Show that he is okay with being second in command, especially since he has been in charge before with his solo music and his role in Lilyhammer. Notwithstanding this, among E Street Band members he often had the second-most amount of "face time" in concert after Clarence Clemons, frequently mugging and posing for the audience and sometimes delivering his unpolished, nasal backing vocals while sharing a microphone with Springsteen. His playing or singing is most prominently featured on the songs "Glory Days", "Two Hearts", "Long Walk Home" (which featured a Van Zandt outro vocal solo during live performances) "Land of Hope and Dreams", "Badlands", "Ramrod", and "Murder Incorporated", among others like the live versions of "Rosalita". He often trades vocals with Springsteen in live versions of "Prove It All Night". He features prominently in the video for "Glory Days", sharing the spotlight with Springsteen during the choruses, while swapping lines with him during the (non)fade, and in live versions he does the same. During the E Street Band's performance at the Super Bowl in 2009, Van Zandt was the most prominently featured member of the band, playing a guitar solo on the final number of the set, "Glory Days," as well as sharing lead vocals and exchanging humorous banter with Springsteen.

Van Zandt was picked to induct The Rascals into the Rock and Roll Hall of Fame in 1997. The original members of The Rascals had been feuding for a number of years and Van Zandt was concerned that the induction and subsequent band performance would result in a very public fiasco on live television. Wanting to defuse any confrontation, Van Zandt donned a Little Lord Fauntleroy-type costume for the event and delivered a humorous induction instead of the more traditional speech delivered for other inductees. The Rascals had worn this type of outfit when they debuted on the national scene in 1965. Chase, a fan of Van Zandt's music, saw this performance on VH1's broadcast of the event, thought Van Zandt was very funny, and contacted him a few days later. It was then that Chase discovered Van Zandt had no acting experience. Van Zandt was reluctant to audition for Chase but eventually relented. His first audition was for the role of the show's main character, Tony Soprano. However, Van Zandt wanted the role to go to a more experienced, "real" actor. The character of Silvio Dante was actually based on a character created for a short story written by Van Zandt.

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. As a guest on the Opie and Anthony Show, Van Zandt tells his casting story to his wide viewer audience on the show:

Since 2002, Van Zandt has hosted Little Steven's Underground Garage, a weekly syndicated radio show that celebrates garage rock and similar rock subgenres from the 1950s to the present day. As of December 2006, the show is heard on over 200 US radio stations and in some international markets. For Example, in Spain it has beamed through Rock & Gol since 2007 and later on Rock FM Radio in Finland; Radio Helsinki started beaming Little Steven's Underground Garage in August 2008.

Van Zandt recorded the narration for The Hives biography on their concert DVD Tussles in Brussels (2004).

In September 2006, Van Zandt assembled and directed an all-star band to back Hank Williams Jr. on a new version of "All My Rowdy Friends Are Coming Over Tonight" for the season premiere (and formal ESPN debut) of Monday Night Football. The all-star lineup included Little Richard, Rick Nielsen (Cheap Trick), Joe Perry (Aerosmith), Questlove (The Roots), Charlie Daniels, Bootsy Collins, Chris Burney (Bowling for Soup), and Bernie Worrell.

Since 2007, Van Zandt has been the Director of a music selection committee for the video game Rock Band; he is in charge of selecting new music for the game.

Van Zandt's song "Under The Gun" was covered by Carla Olson & The Textones on their Detroit '85 Live & Unreleased album which was released in 2008. Another of his songs, "All I Needed Was You", appeared on the 2013 Carla Olson album Have Harmony, Will Travel.

In 2010, Van Zandt appeared as himself in the Norwegian soap opera Hotel Cæsar, broadcast on Norway's biggest commercial channel TV2 Norway. He also appeared on Scandinavia's largest talkshow Skavlan.

On October 20, 2011, the program recorded its 500th show in front of a sold out crowd at the Hard Rock Cafe in New York's Times Square. The guests included the band Green Day; Steve Buscemi, star of The Sopranos and Boardwalk Empire; Vincent Pastore, aka "Big Pussy Bonpensiero" from The Sopranos; actor and Director Tim Robbins; and singer Debbie Harry of the group Blondie.

In 2011, he starred in, co-wrote, and acted as executive Producer on an English and Norwegian language series entitled Lilyhammer, the first original Netflix series that was produced in collaboration with Norwegian broadcaster NRK. The name recalls the city of Lillehammer, which hosted the 1994 Winter Olympics. On the show, Van Zandt portrays a Sopranos-like role of an ex-mafioso who enters the witness protection program and flees to Norway to escape a colleague against whom he testified. The show premiered on NRK television on January 25, 2012 with an audience of 998,000 viewers (one fifth of Norway's population), and ran for three seasons before being cancelled in 2015.

Van Zandt is an Honorary board member of Little Kids Rock, a national nonprofit organization that works to restore and revitalize music education programs in disadvantaged U.S. public schools. He was also awarded the fourth annual "Big Man of the Year" award at the organization's 2013 Right to Rock Benefit Event.

He and his wife Maureen also serve on the Count Basie Theatre's Board of Directors, and were named as that organization's honorary capital campaign chairs in 2015.

Van Zandt reformed his band, the Disciples of Soul, for the first time since 1990 to play their only European show of 2016 at the O2 Indigo Lounge in London for BluesFest on October 29, 2016. The new Disciples included Richie Sambora and Marc Ribler on guitar, Eddie Manion on saxophone, Hook Herrara on harmonica, Leo Green on tenor sax, Richard Mecurio on drums, Jack Daley on bass, Andy Burton on B3 organ, Clifford Carter on piano, Danny Sadownick on percussion, Tommy Walsh and Matt Holland on trumpet, Neil Sidwell on trombone, George Millard on flute, and a women's section called the Divas of Soul (Julie Maguire, Sarah Carpenter and Jess Greenfield) on backing vocals. They played a series of Van Zandt's own solo songs, songs he wrote for Southside Johnny and the Asbury Jukes, a song he co-wrote for the Breakers, cover songs, and "Goodbye", a song that he did with the Lost Boys. He is planning on touring Europe in the summer of 2017 and the United States in the fall. Van Zandt insists that he is not leaving the E Street Band and that he is only touring because the band is not.

He debuted his new album at the annual Rock and Roll for Children event at the Fillmore Theater in Silver Spring, Maryland, on March 18, 2017. Van Zandt debuted a doo-wop song called "The City Weeps Tonight," that was an outtake from Men Without Women. At the end of the show, he covered "Bye Bye Johnny" as a tribute to the late Chuck Berry. According to Backstreets, Van Zandt's new album is going to be called Soulfire, titled after the song he co-wrote for the Breakers. The album was officially released on May 19, 2017.

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