The first public event hosted at the indoor arena was the two-night Born This Way Ball concert of Lady Gaga which began on May 21, 2012.

[15] A separate event was held as part of the grand opening ceremony of the indoor arena held on June 16, 2012; the Icons at the Arena: Masters of OPM which featured various local musicians and singers which was organized by Star Events of ABS-CBN, directed by Johnny Manahan with Ryan Cayabyab as the concert's musical director.

[19] The facility was intended primarily as a venue for concerts and basketball games but can be reconfigured to accommodate other sporting and entertainment events as well.

[20] The structure hosting the events space was designed in a form of an eye which was supported by a slanted podium plinth.

Since 2016, the arena has also hosted Disney on Ice productions every December, except on years that were restricted due to the COVID-19 pandemic in the Philippines.

[26] One Ok Rock was the first Japanese artist to headline a show in the arena, while EXO was the first Korean artist to stage a two-day sold-out concert series in the arena, followed by other K-pop groups such as Big Bang, Blackpink, BTS, 2NE1, Winner, iKON, AKMU, Treasure and Twice.

On October 18, 2012, the arena hosted the National Collegiate Athletic Association's first game of its finals series against the San Beda Red Lions and the Letran Knights.

[34] The SM Mall of Asia Arena was one of the three main venues of the 2016 FIBA World Olympic Qualifying Tournaments for Men, which was held in the Philippines, Italy, and Serbia from July 4–10, 2016.

This is the second FIBA tournament held at the arena[35][36] SM Mall of Asia Arena served as one of the host venues for the 2023 FIBA Basketball World Cup which was hosted by the Philippines from August 25 to September 10, 2023, alongside co-hosts Japan and Indonesia.

The SM Mall of Asia Arena serves as one of the playing venues of the Premier Volleyball League (PVL).

Different generations of the teams between Season 74 to Season 78 came together to play against each other, and proceeds of the game would go to each school's charity foundation, and Rebisco Foundation Inc. Pasay City was one of the host cities for the 2023 FIVB Volleyball Men's Nations League preliminary round, which marked the second straight year the event was held in the Philippines.

[37] The SM Mall of Asia Arena served as the main venue for the Encounter with the Families event, led by Pope Francis during his papal visit to the Philippines on January 16, 2015.

In September 2022, Australian Christian worship band Planetshakers performed at the arena in their first event in the Philippines since January 2020.

On December 9, 2016, Ang Dating Daan celebrated its 36th broadcast anniversary at the arena with a Special Worldwide Bible Exposition.