Thome hit the 550th homer of his career in the eighth inning to put the White Sox ahead and Chicago went on to beat the Oakland Athletics 6-2 on Monday night.
Pierzynski also homered and Scott Podsednik scored two runs for the White Sox, who won for the fourth straight time and have won 10 of its last 13 overall.
Oakland reliever Craig Breslow (1-4) allowed a leadoff walk to Podsednik in the eighth inning. After Alexei Ramirez popped up a bunt attempt, Jermaine Dye singled off Santiago Casilla. On a 1-2 pitch, Thome hit an opposite field home run to left-center to put the White Sox up 5-2.
"He's got almost 600 home runs so he's done it a million times. He's been up there so many times that I don't think it phases him. The guy made a mistake and Jim hit it. The one thing about Jim if he gets the barrel on the ball it can go out to any part of the park. That's why he's got 550 homers," said Pierzynski.
Thome is 13th on the career homers list and has nine this season.
"The bottom line is when the situation like that happens, first of all you got to know what the guy throws and you have to get a pitch to hit. He was throwing me fastballs about 95 in on my hands, luckily I got a slider out over the plate and I was able to put good wood on it," Thome said.
Oakland manager Bob Geren didn't want Casilla to come close to the plate with the 1-2 count.
"He was trying to bounce a breaking ball there and left it right down the middle," Geren said. "That particular pitch he didn't get it where he wanted to. He wanted to get it down and he left it over the middle."
Matt Thornton (3-1) struck out the side in the eighth and the White Sox are back to .500 for the first time since May 3.
"The one thing about this ballclub is when we were losing we did not feel sorry for ourselves. We just kept out head up and continued to play even when it wasn't fun to play," White Sox manager Ozzie Guillen said.
Matt Holliday hit a two-run homer in the first for the Athletics, who have lost five of its last six games and have the worst record in the American League.
Holliday's seventh homer of the season was off White Sox starter Gavin Floyd.
In the bottom of the inning, Podsednik scored on Dye's sacrifice fly. Oakland starter Trevor Cahill escaped further damage when Holliday timed his jump perfectly at the fence to rob Paul Konerko of what appeared to be a two-run homer.
Pierzynski tied the game with a solo shot in the fifth off Cahill.
Cahill worked 5 2/3 innings, allowing two runs on three hits. He had three strikeouts and two walks.
"I thought Cahill had a real nice outing again. He struggled in the first for just a few pitches and then he really settled in and pitched great," Geren said.
Floyd, who was originally scheduled to start Tuesday was pushed up to start Monday so Chicago can give Bartolo Colon an extra day's rest. Guillen decided to give Colon an extra day because of past injuries in his career. The right-hander was limited last season because of bone chips in his right elbow. He is scheduled to start Tuesday against the A's.
Floyd rebounded after the rough first inning, he allowed two runs on four hits in seven innings. He struck out eight and walked three.
RHP Vin Mazzaro will make his major league debut Tuesday night. The A's said Monday they will call up Mazzaro to start the second game of their series against the White Sox. The 22-year-old Mazzaro, a third-round pick in the 2005 draft, was 2-2 with a 2.38 ERA for Triple-A Sacramento. ... Before the game, White Sox GM Ken Williams shot down rumors of trade talks between the White Sox and the Astros regarding RHP Roy Oswalt. "I really try not to get into confirming or denying something because when you start down that road, you set patterns that kind of tip your hand. Whenever you tip your hand, you don't really get anything done. So I'll make the exception so that everyone can kind of relax a little bit. I haven't talked to the Houston Astros about any pitching whatsoever," Williams said.