Before joining The Smiths, Andy Rourke had played guitar and bass in various rock bands, as well as in the short lived funk band Freak Party, often with his school friend John Maher (the future Johnny Marr).

When Marr and Morrissey formed the Smiths, Rourke joined the band after their second gig, and remained with the band almost throughout its existence. Marr claims that Rourke's contribution to The Queen Is Dead LP was "something no other bass player could match". Rourke was briefly sacked from the Smiths over drug abuse, resulting in a weekend prison sentence, which was posted on TV news. The brief dismissal of Rourke came in the form of a note left by Morrissey under the windscreen wiper of his car; "Andy, you have left The Smiths. Good luck and goodbye, Morrissey".

However, in May 1986 Rourke rejoined the Smiths, just before the release of The Queen Is Dead album. Immediately after the break-up of the band, Rourke and Smiths drummer Mike Joyce played with Sinéad O'Connor - Rourke (but not Joyce) appears on the album I Do Not Want What I Haven't Got. They also, along with Craig Gannon, provided the rhythm section for two singles by former Smiths singer Morrissey - "Interesting Drug" and "The Last of the Famous International Playboys" - and Rourke composed the music for Morrissey's songs "Yes, I Am Blind," "Girl Least Likely To," and "Get Off the Stage." Rourke also played bass on "November Spawned a Monster" and "Piccadilly Palare".

Rourke has also played and recorded with The Pretenders (appearing on some of the tracks on 1994's Last of the Independents); Killing Joke, Badly Drawn Boy, Aziz Ibrahim (formerly of the Stone Roses), and ex-Oasis guitarist Bonehead as Moondog One, which also includes Mike Joyce and Craig Gannon.

Rourke and his Production Company with long time Manager Nova Rehman, Great Northern Productions, organized Manchester Vs. Cancer, an anti-cancer concert in Manchester in January 2006. The concert was a response to learning that Nova's father Sheik Abdur, and sister Nina had been diagnosed with cancer. He unveiled Johnny Marr (his old band-mate in The Smiths) as one of the performers taking part.

Rourke is currently in a band called Freebass with bass players Mani (ex-The Stone Roses) and Peter Hook (New Order) and vocalist Gary Briggs. He organized Manchester Vs. Cancer 2007, which took place on March 31st 2007, featuring Noel Gallagher and Gem Archer of Oasis, Paul Weller, Ian Brown, The Charlatans, Echo And The Bunnymen, McAlmont and Butler and former Oasis guitarist Bonehead's new band 'Elektrik Milk'. He also organized the 2008 gig, featuring The Fratellis, The Enemy, Badly Drawn Boy, Inspiral Carpets, Happy Mondays, The View, Athlete and The Farm. A Scottish Vs Cancer event was also held in 2008, featuring The Fratellis, The Proclaimers and more. He has also been playing bass for Ian Brown on his recent tour.

Rourke has recently relocated to New York City. In between DJ gigs he has been in the studio recording new material with Jesse Murphy (formerly of the Brazilian Girls) and Junior Sanchez among others. Rourke also formed JETLAG, his latest studio project, with New York DJ/Producer Ole Koretsky.