The stadium served as the host facility for Super Bowls XXXVIII (2004) and LI (2017), the 2024 College Football Playoff National Championship, and WrestleMania 25 (2009).

The intention was to create a football stadium to replace the Astrodome that would operate like an open-air facility but have the intimacy and comfort of an indoor arena.

[14] During a Texans preseason game on August 30, 2012, against the Minnesota Vikings, an intoxicated fan fell to his death from an escalator.

[21] After hosting Super Bowl LI, further upgrades were made to keep NRG Stadium competitive with other new NFL venues.

[26][27] On December 25, 2024, the first ever halftime show for the NFL's Christmas Gameday is set to be headlined by Beyoncé at NRG Stadium.

[29][30] The Texans' home opener against the Baltimore Ravens was initially postponed one day from Sunday, September 14, 2008, to Monday, September 15, but when the extent of the damage from Hurricane Ike became known, the NFL rescheduled the Texans-Ravens game to week 10 (November 9, 2008), which was to have been the bye week for the Ravens and the Texans' scheduled home game against the Cincinnati Bengals.

[30] The stadium was repaired by Houston-based rope access inspection and construction firm Reel Group Americas on February 13, 2009.

The architects of Populous (then HOK Sport) and the HSC worked together with engineers from Walter P Moore and Uni-Systems to design the stadium utilizing the principles of kinetic architecture.

NRG Stadium has over 7,000 club seats, 186 luxury suites, and multiple lounges and bars.

[11] The stadium can be configured to utilize a 125,000-square-foot (11,600 m2) space for meetings, specialty functions, exhibits, and concerts.

The roof mechanization consists of two large panels that split apart at the 50 yard line, lying over and above each end zone when fully retracted.

Fans in the Bull Pen are encouraged to stand throughout the game, sing, cheer, and otherwise support the team in an enthusiastic manner.

[37] The first regular season game was played on September 8 of that year, where the expansion Texans defeated the Dallas Cowboys 19–10 in front of 69,604.

[38] The first Monday Night Football game in Texans history was held on December 1, 2008 at Reliant Stadium.

NRG Stadium hosted Super Bowl XXXVIII on February 1, 2004 where the New England Patriots defeated the Carolina Panthers, 32–29 in front of 71,525 in attendance.

The bulls, broncs, steers and roping calves are housed in the north end of the stadium under the lower bowl.

Loading and unloading dock space to support the rodeo is located on the north end of the stadium.

[46] On February 25, 2012, the PBR brought its premier bull riding tour, the Built Ford Tough Series, to Reliant Stadium for the first time ever.

A Bayou Classic game between Grambling State and Southern was held here in November 2005 due to Hurricane Katrina damage at the rivalry's usual venue of the Superdome.

[55] In 2017, NRG Stadium was announced as a future site for the College Football Playoff National Championship game; it hosted the event on January 8, 2024 (ending the 2023 college football season), which featured the Michigan Wolverines (winners of the Rose Bowl) and the Washington Huskies (winners of the Sugar Bowl).

[60] In June 2016, NRG Stadium hosted two matches in the group stage and one semifinal in the Copa América Centenario.

For the past eighteen years, NRG Stadium has played host to Monster Jam.

[63] The stadium is a regular concert venue and has featured performers such as The Rolling Stones, Metallica, Beyoncé, U2, Guns N' Roses, One Direction, Taylor Swift, and Coldplay over the years.

[64] Rice University uses executive offices in the stadium to teach a professional sports management class.

During the summer of 2019, the stadium hosted two international conventions of Jehovah's Witnesses, gathering thousands of delegates from around the world.