Ohtani and Mayfield are tied for the team lead with nine home runs since the All-Star break.
“It was an interesting and good baseball game,” manager Joe Maddon said. “The pitchers did well and the offense up and down the lineup did a nice job.”
Despite the longballs from Ohtani and Mayfield, the difference in the game ended up being a two-out single by Juan Lagares off Clay Holmes in the eighth inning that drove in Brandon Marsh with the go-ahead run.
Marsh led off the eighth with a single against Wandy Peralta (4-3) before Lagares delivered his third hit of the night.
The Yankees have dropped three straight for the first time since early July following a 13-game winning streak.
Junior Guerra (5-2), who allowed a prodigious two-run shot to Giancarlo Stanton in the seventh inning that made it 7-all, got the win. Raisel Iglesias, the Angels' seventh pitcher in what was a quintessential bullpen game, struck out DJ LeMahieu, got Anthony Rizzo to ground out and then struck out Aaron Judge in the ninth for his 28th save.
After the Yankees rallied to tie it at 5 in the fifth inning, Ohtani took former teammate Andrew Heaney deep to lead off the bottom half. frame. Ohtani launched Heaney's curveball 432 feet into the second level of the right-field stands.
“I have never seen a ball hit into that level. My goodness, it looked farther than that,” Maddon said.
Ohtani has five hits in 30 career at-bats against the Yankees, with all of his hits leaving the park.
Mayfield's grand slam off Corey Kluber was part of a five-run fourth by the Angels. Mayfield is batting only .227 since being called up in early July, but 14 of his 27 hits have gone for extra bases.
“After I hit it, I blacked out a little rounding the bases. It was definitely an exciting moment in my career. The best thing is we won the game and celebrated after,” Mayfield said.
Stanton had two hits and drove in three runs for the Yankees. He had an RBI single during the fifth inning that tied the game at 5.
ANOTHER STANTON SHOT
Stanton tied it at 7 in the seventh with a two-run drive to center field that caromed off the rocks. The 457-foot homer is the fifth-longest by an opponent at Angel Stadium since Statcast started keeping track in 2015.
The homer also had a 115.2-mile exit velocity. It is only the third time at The Big A that a player has hit a home run over 450 feet with an exit velocity over 115.0. The others are Ohtani and Joey Gallo.
“That was impressive. He went up there with his plan, got a pitch and hit it into the rocks. It was a really big blow for us and we just we just couldn’t finish it off tonight,” manager Aaron Boone said.
MIXED COMEBACK FOR KLUBER
Yankees starter Corey Kluber came off the 60-day injured list before the game and made his first start since May 25. The right-hander, who was sidelined due to a right shoulder strain, didn't give up a hit through three innings and allowed only one walk before things unraveled in the fourth.
Kluber struck out Ohtani to lead off the inning, but then allowed three straight base hits, including an RBI single to Jo Adell. Max Stassi drew a two-out walk to load the bases before Mayfield's grand slam.
“The final line doesn’t look very good, but I think that breaking it down there’s a lot of good to take out of tonight,” said Kluber, who allowed five runs on five hits with six strikeouts and two walks in four innings. “There were a lot of good pitches and not a lot of hard contact. But obviously made a bad pitch in a big spot that ultimately counts for four runs.”
Mike Mayers — who is tied for seventh in the majors with 60 appearances — started for only the second time in his career and gave up two runs in the first, including an RBI double by Rizzo.
The Angels right-hander, whose other start came in 2016 with St. Louis, allowed two runs and three hits in two innings.
Yankees: LHP Zack Britton (left elbow sprain) was moved to the 60-day injured list, which effectively ends his season. Boone said Britton met with Dr. Neal ElAttrache in Los Angeles on Monday to determine if surgery is needed.
Angels: RHP Alex Cobb (right wrist inflammation) threw a 30-pitch bullpen session before the game with the next step remaining to be determined.
The Yankees acquired RHP Jason Parker as the player to be named in the July 27 trade in which the Yankees sent pitchers Luis Cessa and Justin Wilson to the Cincinnati Reds. The 23-year old Parker was 4-3 with a 4.05 ERA with Class A Daytona this season.
Yankees: RHP Jameson Taillon (8-4, 4.18 ERA) has allowed three earned runs or fewer in 11 of his last 13 starts dating back to June 18.
Angels: RHP Jaime Barria (2-2, 5.56 ERA) gets the call after Ohtani was scratched due to soreness in his right hand after being hit by a pitch on Saturday.
Los Angeles Angels' Joe Maddon: Shohei Ohtani didn't mean he wants to leave team
Los Angeles Angels manager Joe Maddon said two-way star Shohei Ohtani didn't mean he wants to leave the organization when he said earlier this week that his top priority is winning.
Los Angeles Dodgers' Albert Pujols goes on COVID-19 injured list; Cody Bellinger (rib) activated off IL
Albert Pujols went on the COVID-19 injured list and Cody Bellinger was activated from the IL after missing eight games with a broken left rib.
Francisco Lindor drives in three as Mets beat Marlins
The Mets win Game 1 of their doubleheader vs. the Marlins thanks to Francisco Lindor's 19th HR of the season.
Lindor, Stroman lead Mets past Marlins 5-2 in DH opener
— Francisco Lindor homered and drove in three runs, Marcus Stroman earned his 10th win and the New York Mets stopped a five-game losing streak with a 5-2 victory over the Miami Marlins in the opener of their doubleheader Tuesday.
Fantasy baseball forecaster: Team hitting ratings
Stay ahead of the game and optimize your fantasy baseball hitters with our forecaster, which provides a rolling 10-day outlook of every team's hitting matchups as well as the potential for stolen bases.
Fantasy baseball forecaster: Pitcher projections for the next 10 days
Keep up to date on who is pitching -- and how well they're expected to do -- with our forecaster, which provides a rolling 10-day outlook of every team's probable starting pitchers with game score projections.