The Reds struck out 12 times against Ivan Nova on Saturday afternoon, but still beat the Yankees 6-5 behind a three-run homer by Joey Votto and 6 1/3 good innings from Homer Bailey.
The Yankees scored twice in the ninth inning and had men at second and third base when Curtis Granderson grounded out to end the game.
"We just didn't get the last hit that we needed to put them away," said New York manager Joe Girardi. "It was good that we came back but frustrating that we didn't win."
Bailey (2-3) snapped a five-start winless streak, striking out seven while giving up three runs on seven hits and a walk.
Votto's three-run homer in the fifth inning broke a 2-2 tie. Mike Costanzo got his first major league hit, a single in the sixth, and had a sacrifice fly in the eighth for what ended up being the game-winning RBI.
"Like I tell the guys all the time, you never know which run you score is going to be the winner," said Reds manager Dusty Baker.
Nova (4-2) had 12 strikeouts in just six innings but lost a decision for only the second time since last June (16-2). He suffered his first interleague loss in five starts (2-1) and the Yankees fell to 6-2 in his outings this season.
The 25-year-old righty allowed five runs on seven hits and two walks. His previous career high was 10 strikeouts against the White Sox last Aug. 4.
Russell Martin and Jayson Nix homered for New York.
The Yankees won the opener of the three-game series 4-0 on Friday behind eight scoreless innings from Andy Pettitte to snap a three-game losing streak. They nearly rallied to make it two in a row.
Raul Ibanez hit a leadoff double against Sean Marshall in the ninth and scored when Nick Swisher followed with a single. Andruw Jones added a one-out base hit to move Swisher to third and Nix's hit through the left side got New York within 6-5.
But Jose Arredondo came in to shut the Yankees down even after Derek Jeter beat out a double-play ball to first. Jeter took second, but Votto fielded Granderson's slow grounder behind first base and beat him to the bag for the last out.
Nova had eight strikeouts through three innings, but also gave up two runs.
Drew Stubbs walked, stole second and scored on a Brandon Phillips single to right in the first inning. In the second, Devin Mesoraco hit a ground-rule double and came around on Chris Heisey's two-base hit for a 2-0 Reds lead.
Martin led off the third inning with his fourth homer of the season, giving the Yankees their first hit.
Nova pushed his strikeout total to nine in the fourth and Ibanez tied the game with an RBI double that scored Robinson Cano in the bottom of the inning.
But the Reds moved back in front on Votto's three-run blast in the fifth, his seventh of the season. Wilson Valdez and Heisey hit back-to-back singles to start the inning and Votto homered to right-center field with one out.
"That really hurt," said Girardi.
Nova fanned Phillips and Jay Bruce to end the inning, reaching 11 strikeouts to beat his old mark, and Nix hit his second homer of the year just over the right field wall in the bottom of the fifth to get the Yankees within 5-3.
Cody Eppley replaced Nova for the seventh, issued a one-out walk and was relieved by Clay Rapada, who picked Stubbs off first base and got Votto on a fly out. Bailey came out with runners on first and second in the bottom of the seventh and Logan Ondrusek got the last two outs.
The Reds then pushed their lead to 6-3 on Costanzo's sacrifice fly off David Phelps.
The Reds traded catcher Koyie Hill to the Chicago Cubs on Saturday for cash considerations. Hill had been batting .195 with three doubles, one home run and five RBI in 14 games for Double-A Pensacola this season...Phelps struck out the side in the top of the ninth...The Reds improved to 3-3 on a seven- game road trip...Arredondo earned his first major league save.