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Horovitz was born on Halloween 1966, and raised on Park Avenue, Manhattan, New York, the son of Doris (née Keefe) and playwright Israel Horovitz. His sister is film producer Rachael Horovitz. His father was Jewish, whereas his mother, who was of Irish descent, was Catholic. He had a secular upbringing.Horovitz began his music career with a stint in the punk rock band The Young and the Useless, who often performed with Beastie Boys. In 1982, Beastie Boys guitarist John Berry quit and Horovitz replaced him. He was only 16 at the time. After Horovitz joined the band, Beastie Boys changed their sound, evolving from a hardcore punk band to a more hip-hop oriented group. The band was signed to Def Jam, and released their debut album Licensed to Ill in 1986. The album was a huge commercial success, and spawned six singles; however, only one would reach the top twenty of the US Hot 100, "(You Gotta) Fight for Your Right (To Party!)" (US #7). The album would eventually be certified diamond several years later. As that song was Beastie Boys' only top twenty US hit in their career, they would technically be a one-hit wonder in the US, however, with a diamond album. Several albums followed, with some attaining platinum or multi-platinum status, and by 2010, Beastie Boys had sold a total of 40 million albums worldwide, with 22 million of those in the US. In 2012, Beastie Boys were inducted into the Rock and Roll Hall of Fame.

In addition to his work with Beastie Boys, Horovitz also remixes numerous tracks for other artists under the alias 41 Small Stars. He plays bass in The Tender Moments, the backing band of New York-based cabaret performer Bridget Everett.

Horovitz has acted in several motion pictures and television shows. Some of his roles include Tim 'Chino' Doolan in Lost Angels (1989), Sam in Roadside Prophets (1992), Repulski in Godspeed (2007), Fletcher in While We're Young (2014), and Nick in Golden Exits (2017).

In 2020, he was featured in the documentary Have a Good Trip.