In the 2005 playoffs, Pierzynski was a major player for the White Sox. In Game 1 of the ALDS against the defending champion Red Sox, Pierzynski would start the White Sox off strong with a 3-run homer in the first inning off of Matt Clement. He would add a second home run in the bottom of the 8th off Bronson Arroyo to help lead the White Sox to a blistering 14–2 win. Pierzynski finished the game 3–3 with 4 RBIs. Pierzynski also hit a double and scored an insurance run in the top of the 9th inning as the White Sox defeated the Red Sox 5–3 to clinch the series and move on to the ALCS. Perhaps Pierzynski's biggest, and most well-known play, came in Game 2 of the ALCS against the then Los Angeles Angels of Anaheim. Down 0–1 in the series and the game tied at 1–1 in the bottom of the 9th inning, Pierzynski famously struck out on a low ball in the dirt from Kelvim Escobar. Thinking they had ended the inning, the Angels proceeded to walk off of the field; however, noting that home plate umpire Doug Eddings had not made the out call, Pierzynski ran down the line to first base and was called safe. Angels catcher Josh Paul and manager Mike Scioscia argued with Eddings but the call stood, and Pierzynski was replaced by Pablo Ozuna, who promptly stole second base. Joe Crede would end the game on a walk-off double to tie the series at 1-1. The White Sox did not lose again, winning the next 3 games in Anaheim to advance to their first World Series since 1959. The White Sox would then sweep the Houston Astros to win their first championship in 88 years, giving Pierzynski his first ring. Pierzynski batted .262 with 3 home runs and 9 RBI, catching all 11 games for the White Sox during their championship run.