The arena was built under the Millennium Dome (renamed The O2), a large dome-shaped building built to house an exhibition celebrating the turn of the third millennium; as the structure still stands over the arena, The Dome remains a name in common usage for the venue.

The arena, as well as the overall The O2 complex, is named after its primary sponsor, the telecommunications company O2, a subsidiary of Virgin Media O2.

[8] On 18 February 2022 during Storm Eunice, large sections of the arena's fabric roof were shredded, causing the evacuation of 1,000 people, and the venue to close.

Ariana Grande was scheduled to perform on 25 and 26 May 2017 as part of her Dangerous Woman Tour, but the event was cancelled after the Manchester Arena bombing on 22 May.

[22] On 26 April 2022, 1970's new wave and rock band Blondie performed a show at the venue as part of their Against The Odds Tour, which featured ten dates across the United Kingdom with Johnny Marr as the support act.

On 15 October 2022, the O2 hosted a boxing match between Claressa Shields and Savannah Marshall that was the first time two female boxers headlined at a major venue in the United Kingdom.

[28] In October 2023, American singer Madonna opened her 40th anniversary concert series, The Celebration Tour, in the O2 Arena.

In May 2024, American singer/songwriter Olivia Rodrigo sold out four shows at the venue, selling over 75,000 tickets on her GUTS World Tour.

English band Keane performed two sold out shows at the venue that month on their Keane20 world tour.

In July 2024, the American band The Killers on the Rebel Diamonds Tour sold out six shows at the venue and selling over 105,000 tickets.

[29] On 24 September 2024, American rock band Linkin Park played their first UK show in 7 years, with new front-woman Emily Armstrong as part of the From Zero World Tour.

It will also host two shows from American Rapper Tyler The Creator on his tour supporting his 8th studio album Chromakopia.