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Wilks has a leading role in the film The Game Changers (2018), a documentary advocating a primarily plant-based diet in high-performance sport and produced by James Cameron.

After starting his pro career with a 5–2 mark in local shows in California, Wilks was chosen to compete on The Ultimate Fighter: United States vs. United Kingdom representing Team UK under coach Michael Bisping. He defeated the highly regarded Che Mills by submission in an elimination match earning him a trip to Las Vegas, Nevada to compete on the show. Wilks had his second fight against Team United States fighter Frank Lester. Wilks won the fight by submission in the second round. In the semi-finals, Wilks faced Lester for a second straight time, after Lester returned to the tournament to defeat David Faulkner while substituting for Jason Pierce, who was removed from the competition by Dana White. In the rematch, Wilks defeated Lester by TKO via knees in the third round, earning a spot in the live finale.

Wilks then faced Peter Sobotta at UFC 115. After three rounds, the fight went to the judges scorecards, which Wilks took 30–27, 30–28, 30–27.

After suffering extensive injuries which included a fractured vertebra and after doctors told him he faced "significantly high risk of paralysis" if he continued to fight, Wilks announced his retirement from active MMA competition on 14 May 2012. His final record, including fights on the Ultimate Fighter TV show, was 10 wins and 4 losses.

Wilks was expected to face Rory MacDonald on 30 April 2011 at UFC 129. However, Wilks was replaced on the card by Nate Diaz.

Wilks made his debut for the UFC winning against DaMarques Johnson at the TUF 9 Finale on 20 June 2009. The fight crowned Wilks as the TUF 9 welterweight champion. Wilks dominated the fight against Johnson showing off strong striking and good submission attempts. Wilks finished the fight with Johnson via a rear naked choke submission in the closing seconds of the first round.

Wilks lost to Matt Brown via 3rd-round TKO, on 14 November 2009 at UFC 105. After being knocked down in the second and being saved by the bell from a submission attempt, Wilks came back early in the third round, attempting a kimura, before losing top position. Brown then, from top position, secured the TKO victory. Prior to UFC 115, Wilks revealed that Brown had broken his orbital bone with an elbow strike after just 30 seconds of the first round.

Wilks was born and raised in Leicestershire, England. He attended Uppingham School. After leaving Uppingham in 1996, Wilks went to Bournemouth University, obtaining a Bachelor of Science degree in Business and Land Management. He moved to the United States in June 2000.

James Brett Wilks (born 5 April 1978) is an English film producer, vegan activist, and former professional mixed martial artist. A professional from 2003 until 2012, he competed for the UFC, King of the Cage, and was the winner of Spike TV's The Ultimate Fighter: United States vs. United Kingdom