The 2021 Fastlane was the sixth Fastlane professional wrestling pay-per-view (PPV) and livestreaming event produced by WWE. It was held for wrestlers from the promotion's Raw and SmackDown brand divisions. The event took place on March 21, 2021, from the WWE ThunderDome, hosted at Tropicana Field in St. Petersburg, Florida. It was WWE's final pay-per-view presented from Tropicana Field during the COVID-19 pandemic as the ThunderDome was relocated to the Yuengling Center in Tampa, Florida due to the start of the 2021 Tampa Bay Rays season. It was the first Fastlane event held since 2019 and the last until 2023. It was also WWE's first pay-per-view event to air on Peacock in the United States, and the last to be available on the standalone version of the American WWE Network before its shutdown on April 4.

Eight matches were contested at the event, including one on the Kickoff pre-show. In the main event, Roman Reigns defeated Daniel Bryan to retain SmackDown's Universal Championship with Edge as the special guest enforcer. In other prominent matches, Drew McIntyre defeated Sheamus in a No Holds Barred match, Seth Rollins defeated Shinsuke Nakamura, Big E defeated Apollo Crews to retain SmackDown's Intercontinental Championship, and Alexa Bliss defeated Randy Orton in an intergender match thanks to the return of "The Fiend" Bray Wyatt following a three-month storyline absence.