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"That was the best knuckleball I've seen him throw since I've watched him. And I've faced him a bunch," Pierzynski said.
"It was just dropping. Moving left, right, up and down. People don't understand how hard it is to hit that. They look up and see 65 mph and they don't really realize how hard it is to actually hit that thing."
On his homer, Pierzynski said he didn't consider it a bad pitch or a mistake.
"I don't remember," he said. "I just saw it and swung and luckily for us it went out and gave us the lead."
Chicago's seventh consecutive victory against Boston and 14th in the past 16 games between the teams denied Wakefield his 200th career victory.
"I felt great. I had a lot of movement on the knuckleball. I just left one pitch up that he hit for a homer ... Just didn't do what it was supposed to do," Wakefield said.
"I thought about it  a little bit before the game, but once I got done with my warm-ups and into the game, I wanted to win for us, not for me personally."
Floyd (9-9) won his third consecutive start. He gave up a run and three hits in seven innings, including a home run to Jarrod Saltalamacchia, and ran his career record against the Red Sox to 6-0.
"I don't know," Floyd said of his success and the White Sox's recent dominance against the Red Sox.
"Minnesota has our number. ... I know that any moment, any game, against any team you do well against or are terrible with can turn right around. You try to ignore that stuff."
Wakefield (6-4) also allowed three hits in seven innings. But his wild pitch in the sixth helped set up the tying run on Paul Konerko's sacrifice fly. And he walked Carlos Quentin to start the bottom of the seventh before Pierzynski drove his fifth home run of the season into the right-center field seats to give the White Sox a two-run lead.
"I know it's going to be tough for us to get to him because from the beginning he was throwing strikes," Chicago manager Ozzie Guillen said of Wakefield. "I know that ball was moving a lot."
The Red Sox played without major league RBI and batting average leader Adrian Gonzalez, a late lineup scratch with a stiff neck. Dustin Pedroia went 0 for 4 and his 25-game hitting streak was snapped.
"I wish we could have come out and swung the bats better for Wake," Pedroia said.
Saltalamacchia worked a 3-2 count off Floyd before hitting his ninth home run to give the Red Sox a 1-0 lead in the third.
The Red Sox threatened in the sixth, loading the bases as Marco Scutaro beat out an infield single and Jacoby Ellsbury and David Ortiz walked before Floyd threw a called third strike past Kevin Youklis.
"The biggest pitch was Youkilis, bases loaded," Floyd said. "I walked a couple of guys to get the bases loaded but being able to execute that pitch and strike him out looking was a key out."
Wakefield held the White Sox hitless through 3 2/3 innings before Adam Dunn singled in the fourth, and Chicago didn't get another hit until Juan Pierre had a bunt single to start the bottom of the sixth. Switch-hitting Omar Vizquel, batting right-handed against the right-handed Wakefield, sacrificed before Pierre made third on a wild pitch. Konerko then delivered his sacrifice fly to left.
- Reliever Jason Frasor, acquired in a trade with Toronto on Wednesday, said he was ecstatic to join the White Sox and be in a pennant race. A Chicago native who has family in the suburbs, Frasor said he wasn't sure what his role would be. He didn't expect to land back in his hometown. "It's nice to be wanted. I think when get traded they always ask, 'Why did I get traded, why me?' I don't feel that way."
- Guillen said he told 44-year-old Vizquel if he keeps playing the way he has for the White Sox he could go another three years in the majors. Vizquel was batting .271 before starting at third base Friday night and the 11-time Gold Glove winner is still a slick fielder, making a couple of nice plays. Guillen also lauded Vizquel's influence on younger players.
- Saltalamaccchia's home run was Boston's 68th on the road this season.
- Youklis, moved from third to first after Gonzalez was scratched, made a nice diving stop on Alejandro De Aza's grounder in the fourth.
- Wakefield is now 7-13 in his career against the White Sox.
- Red Sox manager Terry Francona said Gonzalez should be able to return to the lineup Saturday.