In the first round of the competition, 24 contestants run a four/five-part obstacle course, one at a time. However, during the 'Wipeout Zone', the show takes an epic and serious turn, with the humor dialed down, and serious background music instead of its lighthearted theme music. Generally only those who will pass the first round are introduced, and a nickname is assigned that is used throughout the game. Jill Wagner (and, in Season 5, Vanessa Lachey and the return of Jill in Season 6) offers additional commentary and reactions, and also provides interviews with the contestants filmed before their turn begins. In one of the show's trademarks, the commentators have a humorous running commentary, often mocking and gently insulting the contestants as they compete. The challenges change each week, but always feature offbeat and comical obstacles, such as the 'Sucker Punch', 'Big Balls' (the show's trademark obstacle), the 'Sweeper', the 'Dizzy Dummy' or the 'Dreadmill', and the 'Wipeout Zone'.

In the seventh season, winners from each episode will be brought together for a 'Tournament of Champions' at the end of the season to compete for the title of Ultimate Wipeout Champion. The first round features 24 contestants, while only the top four (top three in season 4 and after) will make it to the final round called the Wipeout Zone, where the winner earns the title of Wipeout Champion and a $50,000 grand prize. During an episode, contestants compete through four rounds of competition until a final winner is chosen.

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