Wilk started his career as a drummer for Greta in 1990, and helped co-found Rage Against the Machine with Tom Morello and Zack de la Rocha in August 1991.

Following that band's breakup in October 2000, Wilk, Morello, Rage Against the Machine bassist Tim Commerford and Soundgarden frontman Chris Cornell formed the supergroup Audioslave, which broke up in 2007.

He briefly played with Pearl Jam shortly after the release of their debut album Ten and had previously been in the band Indian Style with Eddie Vedder.

They quickly achieved commercial success and would go on to release three more studio albums–Evil Empire in 1996, The Battle of Los Angeles in 1999, and Renegades in 2000– before disbanding in October 2000.

[6] On November 1, 2019, it was reported that Rage Against the Machine would be reuniting a second time, and were to perform at the 2020 Coachella Valley Music and Arts Festival before it was canceled due to the COVID-19 pandemic.

After de la Rocha left Rage Against the Machine in October 2000, the remaining members formed Audioslave with former Soundgarden frontman Chris Cornell.

In 2016, Wilk reunited with Morello and Commerford, joining Chuck D, B-Real and DJ Lord to form the supergroup Prophets of Rage.

Wilk and bandmate Tim Commerford contributed in Keenan's side project Puscifer and his album "V" Is for Vagina on the track "Momma Sed".

In 2005, Wilk played the lead role in the independent short movie Sleeping Dogs Lie by writer Chumahan Bowen and director Stuart Lessner.

Wilk performed live with Tom Morello's side project, Street Sweeper Social Club, at the 2010 Coachella music and arts festival.

[17] In late 2013, Wilk joined the band The Last Internationale and recently recorded their debut album called We Will Reign with producer Brendan O'Brien.

[18] To the end of 2014 until June 2015, Brad Wilk was playing drums on tour with the Smashing Pumpkins along with Billy Corgan, Jeff Schroeder and also Mark Stoermer on bass.

On February 26, 2015, while touring Australia with the band, he joined the Foo Fighters on stage at Sydney's Olympic (ANZ) stadium playing drums for a Van Halen cover Ain't Talkin' 'bout Love.