Pierzynski slapped the plate after the collision as the ball got away from Barrett. The Cubs catcher got up, grabbed Pierzynski and punched him. The White Sox's Scott Podsednik, who had been in the on-deck circle, wrestled Barrett to the ground.
White Sox center fielder Brian Anderson, who hit the bases loaded sacrifice fly to score Pierzynski, then got into a fight with Cubs first baseman John Mabry.
Pierzynski, Barrett, Anderson and Mabry were all ejected after a 15-minute delay.
"I asked Michael what happened and Michael said he (Pierzynski) hit him without the ball, but that's baseball to me," Cubs manger Dusty Baker said during an in-game TV interview. "I think Michael is frustrated. Everybody is frustrated and everything broke out."
As Pierzynski went back to the dugout, he raised his hands in the air while a soldout crowd at U.S. Cellular Field roared. He slapped hands with his teammates.
Minutes after the game resumed, the White Sox's Tadahito Iguchi hit a grand slam to give his team a 5-0 lead.
"I think the fight is going to bring us together and (make us) tougher," White Sox manager Ozzie Guillen said.