Founded in 1894, the Tigers had played at the corner of Michigan and Trumbull Avenues in Detroit's Corktown neighborhood since 1896, when Bennett Park opened.

[27] It was part of a downtown revitalization plan for the city of Detroit, which included the construction of Ford Field, adjacent to the ballpark.

[24] The first game at Comerica Park was held on Tuesday, April 11, 2000, with 39,168 spectators attending, on a cold snowy afternoon.

[24] In December 1998, Comerica Bank agreed to pay $66 million over 30 years for the naming rights for the new ballpark.

Ernie Harwell, the team's long time radio announcer and a recipient of the Hall of Fame's Ford C. Frick Award, has a statue just inside the stadium on the first base side.

[37][42][43] Comerica Park is currently the only ballpark in MLB to feature a distinctive dirt strip between home plate and the pitcher's mound.

[44] In the northeastern corner of the stadium behind the stands from the third base line is a Ferris wheel with twelve cars designed like baseballs.

[37] The right field of the stadium features the Pepsi Porch, a picnic deck between the 100 and 200 level seating bowls.

[10] Also in right field, and part of the 100 level seating bowl, is an area of seats known as "Kaline's Corner", an homage to Hall of Fame right fielder Al Kaline, who once played for the Tigers when the team played in Tiger Stadium.

The plan also included new high top tables, a new bar in the middle of the porch, couches and lounge chairs, as well as a fire pit.

[54] In the layout of the playing field at Comerica Park, when a player is at bat, the direction he is facing looks farther to the south than at any other ballpark.

Abreu won the Derby over Tigers catcher Iván Rodríguez, hitting a then record 41 homers during the event.

[62] On August 15, 2011, Minnesota Twins slugger Jim Thome became the eighth player in baseball history to hit 600 career home runs.

[63] Comerica Park hosted its second World Series in 2012, with the Tigers getting swept by the San Francisco Giants.

[64][65] On April 23, 2022, Tigers slugger Miguel Cabrera became the 33rd player in Major League history to get his 3,000th hit with a single in the first inning off of Colorado Rockies pitcher Antonio Senzatela.

[67] Then on July 8, 2023, Matt Manning, Jason Foley and Alex Lange threw a combined no-hitter in a 2–0 victory against the Toronto Blue Jays.

[68] Comerica Park also played host to a near-perfect game by Armando Galarraga against the Cleveland Indians on June 2, 2010.

[120] On July 19, 2017, Comerica Park hosted its first ever soccer game between Roma of the Italian Serie A League against Paris Saint-Germain of France's Ligue 1 in the 2017 International Champions Cup tournament.

[121][122] On July 30, 2023, Crystal Palace of the English Premier League and Sevilla of Spain's La Liga played against each other at Comerica Park.