The relief meltdown started with Eddie Guardado giving up a hard double and single to the first two batters he faced. Both of those runners scored before Quentin got to the plate.
After Juan Uribe doubled and Nick Swisher walked, Rangers manager Ron Washington came out to collect Guardado, who gave up four runs, three hits and a walk in his two-thirds of an inning.
Closer C.J. Wilson came in to try and protect the one-run lead. That's when he threw a first-pitch fastball right down the middle to Quentin.
Calling it a fastball would be too polite, the Rangers closer said.
"It was a meatball," Wilson said. "Call it a meatball. ... We have a big series against Oakland. We have to regroup and get everybody focused and get set up for that.
"I don't make excuses. It had nothing to do with warmups. Me throwing a meatball and he hits a home run, that has to do with me throwing a meatball and a guy hitting a home run."
It was an unfortunate ending to a game that had a few bright spots for the Rangers.
Josh Rupe, Warner Madrigal and Jamey Wright threw 5 1/3 innings of two-run relief after Kevin Millwood left the game with a sore right groin in the second inning. He had already allowed a three-run homer to Jim Thome in the first inning.
It was the third time Millwood had to leave a game with that same groin injury this season. He's also left twice with a bruised right shin.
"[Rupe, Madrigal and Wright] did a great job," Rangers manager Ron Washington said. "The guys that we depend on, we got them to the part of the game that we wanted them in. We just didn't get it done."
The Rangers (52-50) pounced on White Sox starter Clayton Richard early and often. The left-hander was making his Major League debut and lasted only four innings, allowing five runs -- four earned -- on seven hits.
Michael Young hit a solo homer in the first to give the Rangers an early lead, and Texas added two runs in the second and fourth innings to take a 5-3 advantage.
None of it mattered, though, once the fatal eighth inning began. Like Wilson, Guardado wasn't making excuses for his performance.
"I just didn't get the job done, plain and simple," he said. "It's frustrating when things like that happen. The team battles all day. The bullpen battled, the rookie Madrigal came in and battled, Jamey battles, the whole team battles, except myself.
"Everybody is accountable for their actions and I'm accountable. It just didn't work out. It just didn't work out, and -- you hate to say this -- but it was just one of those days. I couldn't find the zone. If I did, I was behind and they hit the ball. You can't do that to a team like this over there because they're playing for something. ... We're playing for something. They got the better end of it. We just have to move forward."
Guardado (1-2) took the loss despite leaving the game with the lead. He was charged with two of the runs that came across on Quentin's homer.
The White Sox (57-43) rally started not long after manager Ozzie Guillen was ejected from the game in the seventh inning for arguing balls and strikes with home-plate umpire Rob Drake.
"We thought we had the game," Washington said. "I mean, you're up 8-5 going into the eighth inning and you bring in your two best relievers, and before you can get out of the inning they got five runs. So it was disappointing, but we've bounced back from disappointments before, and we'll bounce back from this one."
Combined with Oakland's loss to Tampa Bay, the Rangers remain a half-game back of second place in the American League West.