Carlos Santana delivered the game-winning shot, with his 12th home run on a 3-2 fastball down the middle from reliever Dylan Axelrod (3-7) clearing the right-field fence by a few rows. But this game was lost in the ninth more than the 10th.
Jeff Keppinger's two-run, pinch-hit single with the bases loaded off of reliever Cody Allen broke a 3-3 deadlock and gave the White Sox (40-65) a 5-3 lead in the top half of what could have been the final frame. The ball was then handed off to Addison Reed, who has worked just five times in the last 18 days, which is understandable considering the White Sox have lost six in a row and nine of their last 10 contests.
Reed felt great, but the results didn't equal the feeling.
Long sacrifice flies from Michael Bourn and Jason Kipnis tied the game in the bottom of the ninth. It was Michael Brantley's double, pinch-hitter Jason Giambi being hit by a pitch and Drew Stubbs' bunt single that loaded the bases with nobody out and set up Reed's fifth blown save in 31 attempts.
"I didn't make things easy on myself, those first two, three batters," said Reed. "Leadoff double, hit batter, not fielding the bunt cleanly.
"When you let the first three guys on, it's never easy, no matter what the score is. I kind of put myself in my position to where those sac flies score easy runs. [If] those first three guys would not have been on, none of that would have been possible."
Jose Quintana started for the White Sox and battled through five innings of jams to keep his team down just 3-0. Quintana threw 109 pitches, allowing those three runs on seven hits, while striking out six and walking two.
Cleveland scored one in the first on Kipnis' RBI groundout, added one in the fourth on Brantley's double and one in the fifth on Santana's double. But Quintana emerged with his 14th no-decision this season when the White Sox scored three quick runs in the sixth off of Cleveland starter Corey Kluber.
Josh Phegley opened the frame with a single and came around to score one out later on Alexei Ramirez's double. Alex Rios brought home Ramirez with a single, and after Rios advanced to second on the throw home, Adam Dunn's single just to the right of second put the game in a 3-3 deadlock.
It stayed tied until Keppinger came through, Reed's ensuing hiccup and Santana's blast covering 361 feet. That home run gave the victory to Chris Perez (4-1) and was the Indians' third walkoff against the White Sox this season.
"[Bench coach] Sandy [Alomar] was high-fiving [me] when he hit it," said Cleveland manager Terry Francona of Santana's blast. "As soon as he hit it, I was thinking, 'OK, do we bunt him over?' Sandy knows this ballpark better than I do."
Jake Peavy stopped by the White Sox clubhouse a few hours prior to the start of Wednesday's eventual setback, and the way in which his former team lost seemed fitting on his last day before going to Boston. It was Peavy, during an earlier three-game losing streak in Houston, the worst team in baseball by record, who talked to reporters after one loss about how these sorts of losses happening to the White Sox couldn't be made up.
"There's no answer. When things are going bad, they're going bad. Something new every night," Reed said. "Tonight, it was 100 percent my fault. Just got to hang with them and get after them tomorrow. I don't think any of us have an answer for it or else we would have changed and figured it out.
"But it's part of the game. I wish I knew how to fix it or what to do about it."
General manager Rick Hahn took steps toward turning things around by moving veterans Matt Thornton, Jesse Crain and Peavy before Wednesday's non-waiver Trade Deadline, starting to develop a younger core and gain greater financial flexibility for future changes. While Ventura would never blame his team's season-long poor play on the pressure of trade rumors, he was hoping things would get better Wednesday.
"I'm not blaming everything that has happened on this just because of the Trade Deadline," Ventura said. "You hope that's the case, where they go out there and maybe they don't have that subconscious thought of they might not be here in a couple of days. Hopefully, it's better."
There's always tomorrow's series finale, which might be the new White Sox mantra in this forgettable campaign.