It was primarily the home of the Detroit Lions of the NFL from 1975 to 2001 and was also home to the Detroit Pistons of the National Basketball Association (NBA) from 1978 to 1988. In addition, the Silverdome also served as the home venue for the Detroit Express of the North American Soccer League and the Michigan Panthers of the United States Football League, as well as two college bowl games: the Cherry Bowl and the Motor City Bowl. In 2012, the Silverdome served as the home venue of the Detroit Mechanix of the American Ultimate Disc League and hosted the league championship game that season.

The stadium was a regular concert venue and hosted a number of athletic and non-athletic events, including the 1979 NBA All-Star Game, Super Bowl XVI, WrestleMania III, early round games of the 1994 FIFA World Cup, and regional games in the NCAA Division I Men's Basketball Tournament.

After the opening of Ford Field in 2002, the stadium was left without a permanent tenant. The city of Pontiac was unable to find a good use for the stadium, leaving it empty for 8 years; the city ran out of money, and was forced to sell due to the rising maintenance costs. After multiple attempts to solicit redevelopment plans, the city eventually sold the stadium at auction in 2009 with no reserve for $550,000 (less than 1% of the cost to build the dome) to a Canadian real estate developer. After a significant financial investment by the new owners, the facility was brought back to its original glory. The millions of dollars invested by the new owners were needed to bring The Silverdome back to a safe and clean facility. The property fell into disrepair brought on by the city's financial crises, and The City of Pontiac's inability to afford to spend the necessary capital investments it required. The Pontiac Silverdome reopened in 2010 and hosted many events, including soccer matches, concerts, HBO championship boxing, monster truck shows and many more. The harsh Michigan weather eventually got the best of the aging venue, and in 2013 an excessive amount of snow caused a portion of the antiquated roof system to tear. The Pontiac Silverdome's roof issues dated back to the 1980s with a long list of weather related problems. The Pontiac Silverdome's uniqueness was also its downfall. As one of the last air supported football stadiums left, the inability to find a qualified company capable enough to repair the damaged roof, paired with the financial woes of the city, and the city's inability to pay for police, emergency services and road maintenance, the decision to close the facility for good was decided in 2013. The owners later auctioned the stadium's contents in 2014 and for a few years the parking lot was home to tens of thousands of recalled Volkswagen vehicles.

In 2017, the Silverdome owner decided to tear down the closed facility. The upper ring of the stadium, which had supported the roof structure, was imploded on December 4, 2017, after a failed attempt the previous day. Following the implosion, the remains of the stadium were brought down in sections with hydraulic excavators, and the last free standing section was felled by late March 2018. In September 2019, it was announced that Amazon would develop the site.

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