Every year since the stadium was built, the New South Wales rugby league team's home games in the State of Origin series have been played there. Also the stadium has since hosted the annual National Rugby League grand final. ANZ Stadium also hosted the 2003 Rugby World Cup finals and Bledisloe Cup matches, regular Sydney Swans and Greater Western Sydney Giants AFL matches, as well as international soccer matches featuring Australia's national team the Socceroos, and exhibition games by Sydney based A-League team Sydney FC. The stadium also hosted the 2015 AFC Asian Cup final.

The stadium was originally built to temporarily hold 110,000 spectators, making it the largest Olympic Stadium ever built but still not the largest in Australia, with the MCG formerly holding more than 120,000 before its re-design in the early 2000s. In 2003 reconfiguration work was completed to shorten the north and south wings, and install movable seating. These changes reduced the capacity to 83,500 for a rectangular field and 82,500 for an oval field (making it the second largest stadium in Australia, after the Melbourne Cricket Ground). Awnings were also added over the north and south stands, which allows most of the seating to be undercover. The stadium was also engineered along sustainable lines for example with the low use of steel in the roof structure in comparison to the Olympic stadiums of Athens and Beijing.