The University of Phoenix, a for-profit university specializing in adult education, acquired the naming rights in September 2006, shortly after the stadium had opened under the name Cardinals Stadium. The "University of Phoenix" name is applied as a corporate sponsor, and not as the home stadium of the University (which has no intercollegiate athletics program).

The 63,400-seat stadium (expandable to 72,200) opened on August 1, 2006 after three years of construction. It is considered an architectural icon for the region and was named by Business Week as one of the 10 “most impressive” sports facilities on the globe due to the combination of its retractable roof (engineering design by Walter P Moore to a scheme design by Buro Happold) and roll-in natural grass field. It is the only American facility on the list. The ceremonial groundbreaking for the new stadium was held on April 12, 2003.

The cost of the project was $455 million. That total included $395.4 million for the stadium, $41.7 million for site improvements, and $17.8 million for the land. Contributors to the stadium included the Arizona Sports and Tourism Authority ($302.3 million), the Arizona Cardinals ($143.2 million), and the City of Glendale ($9.5 million).

The first preseason football game was played August 12, 2006 when the Cardinals defeated the Pittsburgh Steelers, 21-13. The first regular season game was played September 10 against the San Francisco 49ers (the Cardinals won 34–27). The stadium's air-conditioning system made it possible for the Cardinals to play at home on the opening weekend of the NFL season for the first time since moving to Arizona in 1988.

The stadium hosted the highest attended soccer match in the state of Arizona on February 7, 2007 when 62,462 fans watched the United States men's national soccer team defeat Mexico, 2–0.

The multipurpose nature of the facility has allowed it to host 91 events representing 110 event days between the dates of August 4, 2006 through the BCS National Championship January 8, 2007. These events included Arizona Cardinals games; public grand opening tours held August 19 & 20, 2006 (attended by 120,000 people); various shows, expositions, tradeshows and motor sport events; the Rolling Stones concert November 8 2006; the AIA 4A and 5A state championship games for football (the first high school to win a football championship at the stadium was Cactus Shadows High School of Cave Creek, AZ on December 2, 2006); an international soccer exhibition match; the Fiesta Bowl National Band Championship High School Marching Band competition (the first marching band to ever play on the field was Foothill High School, from Pleasanton, California on December 29, 2006); the Fiesta Bowl January 1, 2007 featuring the Boise State Broncos vs. the University of Oklahoma Sooners (Boise State won 43-42 in overtime); and the BCS National Championship January 8, 2007 between the No. 1 Ohio State Buckeyes and the No. 2 University of Florida Gators, which the Gators won 41-14. It also held the 2008 Fiesta Bowl between the Oklahoma Sooners and the West Virginia University Mountaineers, as well as the 2009 Fiesta Bowl between the Texas Longhorns and the Ohio State Buckeyes. It has also held many high school graduations.

The Cardinals' first home playoff game since the 1940s took place at the stadium on Jan. 3, 2009, with Arizona beating the Atlanta Falcons, 30-24. The stadium also hosted the 2008-09 NFC Championship Game between the Cardinals and Philadelphia Eagles on Jan. 18, 2009, which the Cardinals won 32-25 in front of 70,650 fans in attendance.

The stadium has 88 luxury suites — called luxury lofts — with space for 16 future suites as the stadium matures.

The 25 acres (100,000 m2) surrounding the stadium is called Sportsman's Park. Included within the Park is an 8-acre (32,000 m2) landscaped tailgating area called the Great Lawn.

There are no obstructed view seats in the stadium. There are visible areas in the upper deck of the end zone where seats could have been put in but were not due to the giant super columns supporting the roof structure.