Similar in premise to shows such as Whose Line Is It Anyway?, the series puts two teams of comedians against each other in a series of Wild 'n Out games which are all basically "improvisational" comedy games. The Teams are the "Red Squad", which was the team name until Season 5 where they became the "Platinum Squad" and were permanently captained by Cannon; and the "Black Squad", led by a celebrity guest until Season 7 where the situation was reversed with Cannon becoming the Black Squad team captain and the celebrity guest leading the Platinum Squad.

For Season 8, the colors were revamped once again with the Gold Squad replacing the Black Squad. The Gold Squad was led by Cannon while the celebrity guest remained captain of the Platinum Squad. For Seasons 9–14, Cannon led his original Red Squad team color while the Black Squad team color returned also.

For Season 15, the teams were revamped as Nick Cannon leads the Old School team, comprising older cast members and a legendary special guest, and the celebrity guest lead the New School Team, comprising some newer cast members.

For Season 16, the teams changed once again. In a format similar to Old School vs New School, Nick Cannon leads Team Revolution and the celebrity guest, appearing as a hologram, leads Team Evolution.

For Season 17, it's reverted back to the "Old School" vs. "New School" format. Nick Cannon and a legendary special guest leads the "Old School" team, and the celebrity guest lead the "New School" team.

For Season 20, was reverted back to the "Red Team vs Black Team" format, Nick Cannon leads the Red Team and the celebrity guest lead the Black Team.

For Season 21, it’s reverted back to the "Old School" vs. "New School" format, Nick Cannon and a legendary special guest leads the "Old School" team, and the celebrity guest leads the "New School" team.

After three such games, the two teams square off against each other in the final round of the game called 'WildStyle', in which they must deliver a punchline directed at their opponent's team member(s) within a freestyle rap. The comedians "beef" with each other; however, some are impersonal jokes. Although similar to Whose Line, the "points don't matter", the teams score one point per round victory during the normal rounds, plus one point per favorably judged punchline during 'Wild Style', which makes it similar in format to the improv show ComedySportz.

Each episode also includes a musical performance, occasionally by the guest captain for the Black/Platinum Squad (Nick Cannon performed with Migos in Season 6 in the episode featuring Chanel Iman). At times, the musical guest comes out just before 'Wild Style' as the judge for the beefs. Starting with season 2, the teams now compete for a "Wild 'N Out" Championship belt (Million Dollar Chain in Season 16 and 17) which if the celebrity guest team w…

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In November 2012, it was announced that the series would be returning in 2013 after a six-year hiatus. The revival features celebrities, along with the show's current cast. The fifth season premiered on MTV2 to 1.1 million total viewers, making it the highest-rated telecast in the network's history. The show would continue on MTV2 for three seasons.

On June 9, 2016, Wild 'N Out was renewed for an eighth season, which would mark the series' return to MTV. The season premiered on August 4, 2016.

In April 2019, the series was renewed through Season 16. On June 19, 2019, it was announced that Wild 'N Out would expand to VH1, with a special Summer season premiering on July 7, 2019.

On July 14, 2020, Nick Cannon was fired by ViacomCBS after making racist and anti-Semitic remarks during an episode of his podcast Cannon's Class with Professor Griff. Cannon endorsed conspiracies about Jewish control of finance, claimed that Jews had stolen the identity of "black people as the 'true Hebrews'" and cited Louis Farrakhan, who is labeled as an anti-semite by the Southern Poverty Law Center and Anti-Defamation League.

Cannon called white people "savages" who were "closer to animals", claiming the "only way that they can act is evil", citing the pseudoscientific melanin theory. A statement from ViacomCBS noted that the company's relationship with Cannon was terminated due to his promotion of "hateful speech and ... anti-Semitic conspiracy theories". Two days later, Cannon released an apology for his remarks regarding anti-Semitism: "I want to assure my Jewish friends, new and old, that this is only the beginning of my education." He demanded complete ownership of Wild 'n Out and an apology from ViacomCBS for his termination.

Upon being made aware of his comments on the podcast, Fox consulted Cannon and accepted his public apology, allowing him to remain host of The Masked Singer. He donated his first paycheck to the Simon Wiesenthal Center. On February 5, 2021, ViacomCBS announced that Wild 'N Out would resume production with Cannon as host, stating that Cannon had "taken responsibility for his comments" and "worked to educate himself" through conversations with Jewish leaders. New episodes began airing on April 6 that same year.