He has previously played in Major League Baseball (MLB) for the San Diego Padres, Los Angeles Dodgers, Milwaukee Brewers, Chicago White Sox, and Pittsburgh Pirates.

[1] Grandal was rated as one of the top defensive catchers heading into the 2007 Major League Baseball draft, but there were some questions about his hitting ability.

[6] He was the Atlantic Coast Conference Player of the Year[1] and finished second for the Golden Spikes Award behind Bryce Harper.

[10] On December 17, 2011, the Reds traded Grandal, Edinson Vólquez, Yonder Alonso, and Brad Boxberger to the San Diego Padres for Mat Latos.

[12] Grandal was the third catcher on the Padres' 40-man roster at the time, behind Nick Hundley and John Baker on the depth chart.

After batting .317 with a .421 OBP and four home runs, 23 RBIs in 120 at-bats, Grandal was promoted to San Diego as they needed another batter on the bench.

[15][16] He made his major league debut on June 2, 2012, entering as a defensive replacement and flying out in his only at-bat against the Arizona Diamondbacks.

[19] In his first major-league start, just hours after being recalled from Tucson on June 30, 2012, Grandal became the first player in MLB history to homer from both sides of the plate for his first career hits in the same game (against Colorado Rockies pitchers Christian Friedrich and Jeremy Guthrie).

He was also the second Padre to have a pair of home runs in his first career start since Keith Lockhart accomplished the feat in 1994, and the fourth in team history to do it from each side of the plate in a single contest.

[24][25] In a January 2013 report, he, along with several other Major League Baseball players, was linked to Biogenesis of America, a clinic that allegedly produced performance-enhancing drugs.

[28] On December 18, 2014, he was traded to the Los Angeles Dodgers (along with Joe Wieland and Zach Eflin) in exchange for Matt Kemp, Tim Federowicz and $32 million in cash.

[29] On May 7, 2015, Grandal hit two three-run homers and recorded a career high eight RBIs in a game against the Milwaukee Brewers.

[30] On June 21, Grandal became the first Dodgers catcher with two home runs and a bunt single in one game since Roy Campanella on August 30, 1955.

[34] He had arthroscopic surgery on his shoulder at the conclusion of the season[35] and signed a one-year, $2.8 million, contract with the Dodgers, to avoid salary arbitration.

[51] On July 24, 2020, Grandal was the starting catcher, making his White Sox debut on Opening Day against the Minnesota Twins.

[54] On August 27, 2021, in his first game since being reactivated, Grandal hit two home runs and tied a White Sox record with eight RBIs in a 17–13 win over the Chicago Cubs.