[8] The arena is well known for numerous professional boxing superfights, such as Evander Holyfield vs. Mike Tyson I and II, Oscar De La Hoya vs. Floyd Mayweather Jr., Oscar De La Hoya vs. Manny Pacquiao, Manny Pacquiao vs. Juan Manuel Márquez IV, Floyd Mayweather Jr. vs. Canelo Álvarez, Floyd Mayweather Jr. vs. Manny Pacquiao, Deontay Wilder vs. Tyson Fury II, Canelo Álvarez vs. Caleb Plant and Kostya Tszyu vs. Zab Judah.

On September 7, 1996, the Bruce Seldon vs. Mike Tyson bout was held here; later that night, rapper Tupac Shakur (who attended the fight) was shot in a drive-by attack.

The fight continued to the 12th round and Mayweather won by unanimous decision and became the unified welterweight champion of the world.

It also previously served through 2015 as the pre-season home for select Los Angeles Kings games against the Colorado Avalanche, Phoenix Coyotes and San Jose Sharks, known as Frozen Fury.

From 2014 to 2017, the MGM Grand Garden Arena hosted the Roman Main Event, then called The MGM Resorts Main Event, an 8-team college basketball tournament held during Monday and Wednesday of Thanksgiving week of NCAA Division I men's basketball season.

The venue was a consistent site for the Academy of Country Music Awards and has served as host twelve times since 2006, including 2018's event which was the first following the 2017 Las Vegas shooting, which occurred roughly 1 mile away.

On October 31, 2016, the band covered David Bowie's The Rise and Fall of Ziggy Stardust and the Spiders from Mars in its entirety as their musical costume for the evening.