The game was marred by a bench-clearing brawl in the fifth inning and a total of five ejections, with the Chicago defeat allowing the Minnesota Twins (62-49) to leapfrog them in the division after their 6-2 home win over Cleveland.
The fireworks started when Kansas City catcher Miguel Olivo was hit in the wrist by a pitch from Chicago's D.J. Carrasco.
Olivo charged the mound appeared to be preparing to punch Carrasco, a former Royals pitcher, when Chicago catcher A.J. Pierzynski grabbed him from behind.
The Royals catcher responded by hitting Pierzynski in the head, with both dugouts and bullpens emptying on to the field after Olivo made his rush to the mound.
Carrasco, Olivo and White Sox manager Ozzie Guillen were all ejected, after Kansas City manager Trey Hillman and Royals starter Zack Greinke were earlier tossed from the game.
Olivo told reporters he was convinced the White Sox were throwing at him.
"They come inside hard three times," Olivo said.
"That is the team that has hit me three times already. It seemed so obvious to me.
Guillen in turn blamed Olivo for the brawl.
"Olivo overreacted to the situation," Guillen said. "I'm not going to bring a guy in that throws 85 miles an hour to hit somebody."
Pierzynski defend his team and his manager after the incident, which came a half inning after Hillman and Greinke were ejected after Greinke hit Chicago's Nick Swisher with a pitch.
"We don't play like that," Pierzynski said. "Ozzie doesn't play like that. This team doesn't play like that."
Mike Aviles went 4-for-4 with a home run and Jose Guillen also homered for the Royals, who pounded out a season-high 19 hits for the second straight game. Greinke pitched 6 1/3 solid innings for the win before he was ejected.
Sunday's game was the finale of a 10-game road trip for the White Sox, who lost two of three games to the fourth place Royals. Chicago (61-49) now heads home for the next 10 games, where the Sox are 35-16.
