Mark Trumbo hammered a game-winning home run in the bottom of the ninth inning to lift the Angels over the Yankees, 9-8, in the opener of a three-game set at Angel Stadium.
Trumbo finished with three hits, two RBI and three runs scored, while Kendrys Morales and Howie Kendrick each knocked in three runs for the Angels, who stretched their season-high win streak to seven games.
Jordan Walden (2-1) earned the win with two scoreless innings of relief.
But there was some bad news earlier in the contest when Angels star pitcher Jered Weaver was forced to leave the game in the first inning with a lower back injury.
Cory Wade (0-1) gave up Trumbo's leadoff blast to suffer the loss for New York, which had its five-game win streak snapped.
Phil Hughes started the game for the Yankees and allowed seven runs on 11 hits with no walks over 5 1/3 innings.
"It was a struggle for [Hughes] tonight. We had chances. It was a game we continued to fight back, then the game was over," Yankees manager Joe Girardi said. "It happened quick. Trumbo has that type of power."
New York entered the seventh inning trailing, 8-5, but was able to tie the game after loading the bases with no outs on a Robinson Cano double, a Mark Teixeira walk and a single by Raul Ibanez off new pitcher Jason Isringhausen, who replaced David Carpenter on the bump.
Nick Swisher brought home the first run of the inning on a sacrifice fly to left and after Eric Chavez's groundout to first placed runners on second and third, Russell Martin pulled a double down the third-base line to score Teixeira and Ibanez.
Derek Jeter's groundout to short ended the inning and kept the score 8-8.
The Angels had a chance to retake the lead in the bottom of the seventh, but left a man on second when Mike Trout flied out to right.
New York had its own chance to take the lead by loading the bases with two outs in the top of the ninth on a Teixeira base hit, a walk by Chavez and an infield single by Martin, but Walden escaped the inning with a grounder off the bat of Jeter.
It then took Trumbo just three pitches in the bottom of the frame to end the game when he pulled an inside changeup around the left-field foul pole for the winning blast.
"It was a changeup. I wasn't looking for it," said Trumbo. "I tried to put it in the air and you saw what happened. It was an awesome feeling. I couldn't be happier."
The Yankees jumped out to a three-run lead in the first inning on a pair of errors by the Angels.
After Jeter and Curtis Granderson started the game with back-to-back singles, Alex Rodriguez hit a grounder to short that Erick Aybar misplayed, allowing Jeter to score from second and placing runners on the corners.
Cano stepped up next and during the second pitch of the at-bat, Weaver appeared to injure himself while throwing a strike.
He was immediately looked at by trainers and attempted a warm-up pitch, but he was in obvious discomfort on his follow through and was replaced by Bobby Cassevah on the mound.
"I've never felt like that before. It felt like someone stabbed me in the back," Weaver said about his injury. "As I released the ball, I couldn't bend over. I don't have any answers. It's pretty painful right now. I'll have an MRI tomorrow."
Cano eventually struck out, but Teixeira followed with a walk to load the bases. Ibanez then lifted a sacrifice fly to left, plating Granderson.
Swisher followed with a grounder back to the mound that could have limited the damage, but Cassevah's throw to first was wide, allowing Rodriguez to score and placing runners on second and third.
Chavez was then intentionally walked to load the bases before Martin flied out to center field to end the inning.
The lead was shortlived, however, as the Angels answered in the bottom of the frame to go on top.
Trout led off with an infield single and Albert Pujols later had a base hit to place runners on the corners.
Morales stepped up next and singled in Trout before Trumbo slapped a ground- rule double to right to bring home Pujols. Kendrick followed with a two-run single up the middle to give the Angels a 4-3 lead.
The Yankees were able to knot the game at four in the second on Granderson's solo blast over the right-field wall, but the Angels regained a one-run advantage in the third.
Trumbo led off the inning with by sending a ball into the right-center field gap that Granderson seemed to track down, but he was crashed into by Swisher as soon as the ball hit his glove. The center fielder couldn't hang on and Trumbo reached third base with a triple. Kendrick stepped up next and lifted a sacrifice fly to right to hand the Angels a 5-4 edge.
The teams traded solo shots by Trout and Teixeira in the fourth and fifth innings, respectively, to keep it a one-run game.
Peter Bourjos singled and advanced to second on a Bobby Wilson sacrifice bunt in the sixth inning before Hughes was replaced on the mound by Cody Eppley, who loaded the bases with two outs on a base hit by Maicer Izturis and a walk by Pujols.
Eppley was then replaced by David Phelps and Morales greeted the new pitcher by slapping a two-run double into the left-center field gap to give the Angels an 8-5 lead.
Hughes has allowed at least one home run in 10 straight starts...Weaver was charged with three unearned runs on two hits in his brief outing...The season series between the teams is tied, 2-2...New York went 3-for-11 with runners in scoring position and left 11 men on base...The Angels hit 5-for-9 with runners in scoring position and stranded eight.