The stadium opened on April 4, 2006 with an exhibition between the minor league Memphis Redbirds and Springfield Cardinals, both affiliates of the St. Louis Cardinals, which Springfield won 5–3 with right-hander Mike Parisi recording the first win. The first official major league game occurred on April 10, 2006 as the Cardinals defeated the Milwaukee Brewers 6–4 behind an Albert Pujols home run and winning pitcher Mark Mulder.
To date, the largest attendance for a baseball game occurred Mothers Day May 12, 2019 with an attendance of 48,556 in a game between the Cardinals and the Pittsburgh Pirates.
In 2004, then Anheuser-Busch president August Busch IV announced the brewing-giant purchased the 20-year naming rights for the stadium. Team owner William Dewitt Jr., said: "From the day we began planning for the new ballpark, we wanted to keep the name ‘Busch Stadium.' August Busch IV and Anheuser-Busch share our vision for continuing that tradition for our great fans and the entire St. Louis community."
The stadium is the third stadium in St. Louis to carry the name Busch Stadium. Sportsman's Park was renamed Busch Stadium in 1953. Team owner August Busch Jr. had planned to name it Budweiser Stadium, but league rules prohibited naming a venue after an alcoholic beverage. Busch named the stadium after himself and later created Busch Beer. The first Busch Stadium closed in 1966 and both the baseball Cardinals, and the National Football League (NFL)'s team of the same name (now the Arizona Cardinals) moved to a new multi-purpose stadium, named Busch Memorial Stadium (Busch Stadium II).
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