This showing by the 38-year-old Griffey caught the eye of the Royals' 22-year-old Billy Butler.
"He was one of my idols growing up -- my first baseball card, Ken Griffey Jr. Eight years old and I even paid with my own chore money for it," Butler said.
"He was my favorite player and it's just awesome to see him play. He did some damage against us, but you don't get to see a future Hall of Famer play every day."
On the Royals' side, two botched plays in the middle of the infield contributed to the loss. To spread more gloom, both second baseman Mark Grudzielanek and DeJesus suffered ankle injuries that took them out of the game.
Grudzielanek's injury appeared more serious, although there was no fracture.
The outcome was decided by the White Sox three runs in the sixth inning off rookie right-hander Luke Hochevar.
Carlos Quentin lined a single, and with two outs, Alexei Ramirez's grounder up the middle was muffed by Grudzielanek behind the mound. It was scored a single and kept the inning alive.
Up came Griffey, obtained on Thursday from the Reds. He had singled off Hochevar in his first White Sox at-bat to score Jim Thome in the second inning. He'd hit that long out, too, in the fourth so he was a formidable presence to be sure.
"Yeah, I mean he's a good hitter and he's been in the game for a long time," Hochevar said. "For a transaction that happens that quick, I was able to see very limited film on him. Then again, I watched him growing up my whole life."
It didn't help. Griffey grounded a single into right field to score Quentin.
Now Nick Swisher hit a bouncer that sent shortstop Mike Aviles into the hole. He got the ball, looked to second base but Grudzielanek was nowhere close to the bag. Aviles had to eat the ball and it went for an RBI single.
"Grud's in the right spot," Royals manager Trey Hillman said. "There's no play at second base, simply because the second baseman can't get there because of the defensive positioning for the hitter."
Aviles and Grudzielanek both had shifted toward right field for Swisher, batting lefty against Hochevar.
"In that situation, I've got to remember that I'm shifted over toward the middle and so is he. That's the kind of mistake that shouldn't happen and won't happen again," Aviles said.
Juan Uribe followed with an RBI single up the middle and White Sox starter Javier Vazquez had a 4-0 lead.
Then the Royals broke through with two runs off Vazquez in their half. Aviles walked, Grudzielanek singled, Butler singled in a run and Alex Gordon lofted a sacrifice fly.
But that was all the Royals would get after a bunt play went awry in the bottom of the seventh. Ross Gload singled and John Buck walked to stir promise, but Esteban German couldn't get down a sacrifice bunt.
German even tried to bunt, on his own, with a full count and fouled reliever D.J. Carrasco's pitch for a strikeout.
"It was just a situation where Hermie was just asking himself to do too much. The bunt sign wasn't on on a 3-2 count," Hillman said.
Mitch Maier, who replaced DeJesus, and Aviles each grounded out to end the threat. There were no more baserunners for the Royals.
Afterward, Griffey was asked if he was nervous in his first game for the first-place White Sox.
"Jermaine [Dye] asked me that in the seventh inning. I said I'm still nervous," he said.
Of course, by then he'd already done enough damage to sink the Royals.
Grudzielanek was forced to leave in the ninth after colliding with teammate Gload on a popup. Grudzielanek held on to make the catch on the play.