The 3-4-5-6 hitters in Texas' lineup combined to go 7-for-20 with three doubles and seven RBIs.
"What was nice was to see the middle of my order come up big," manager Ron Washington said. "We need that. Without those guys doing what they did and what they are capable of doing, it would be a long year. They pulled it out for us tonight."
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Rangers rookie Justin Grimm pitched just well enough to beat Pettitte, and the AL West leaders won for the seventh time in nine games following a six-game slide -- their longest of the season. Texas improved to 6-12 against the Yankees since the start of 2011, both perennial playoff teams this decade.
Lyle Overbay and Ichiro Suzuki homered for New York on a hectic day at Yankee Stadium, where baseball's most famous franchise announced that first baseman Mark Teixeira needs season-ending surgery on his right wrist.
Manager Joe Girardi and general manager Brian Cashman also discussed the latest Alex Rodriguez drama, and the team said all parties involved are on the same page about posting injury updates on Twitter after A-Rod called Cashman for a clarification chat.
Grimm (7-5) allowed three runs in five-plus innings for his second straight win over a 2012 division champion.
"I guess a win's a win," he said. "I'd just love to be able to go deeper in the game, especially when I'm cruising like that, going at guys."
Pettitte (5-6) settled in after a rocky third but dropped his third start in a row since earning his 250th win. He has struggled since coming off the disabled list June 3 and is 2-6 in his past 10 starts since winning his first three of the season.
"My body is feeling good, my velocity is good, my command is good," Pettitte said. "It will turn. I've been through this before and it's worked out all right. I just want my body to keep feeling good."
Cruz, with little success against the Yankees in recent years, hit a two-run shot off struggling reliever Joba Chamberlain in the seventh to extend Texas' lead to 6-3 and tie a club record with his fifth consecutive 20-homer season.
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Suzuki's two-run drive in the bottom half was a no-doubter into the second deck in right, the first homer all season off left-handed reliever Robbie Ross.
Not known for his power, Suzuki also hit a game-ending homer in the series opener Tuesday.
Tanner Scheppers worked a perfect eighth, one night after serving up Suzuki's clutch home run. Joe Nathan got three quick outs for his 26th save in 27 tries.
"Last night was a little tough to swallow," Beltre said. "But today we came back with a better attitude."
Overbay, the replacement for Teixeira, hit his ninth homer to the back of the Yankees' bullpen in right-center to give Pettitte a 1-0 lead in the second. But the left-hander, making his second start since turning 41, gave it right back.
A bunt single by Leonys Martin and a throwing error by third baseman Jayson Nix on Elvis Andrus' sacrifice helped Texas load the bases in the third. Beltre doubled off the left-field wall on an 0-2 delivery and Pierzynski hit the next pitch to right-center, making it 4-1.
"Obviously, when Nellie and Adrian are swinging the bat well, it makes my job hitting behind them a lot easier," Pierzynski said. "But I think this team has prided itself on 1 through 9 giving you tough at-bats, and I think that we've kind of started to get healthy and guys have started to do that."
After a visit from pitching coach Larry Rothschild, Pettitte retired his next 10 batters and did not permit another run. He yielded three earned runs and six hits in six innings, striking out six.
Robinson Cano and Travis Hafner hit consecutive RBI singles off Ross in the sixth, cutting it to 4-3. The Yankees then loaded the bases, but Nix grounded into an inning-ending double play.
"We closed their lead a couple of times. They've been really good. Tonight we gave them extra opportunities and they really cost us," Girardi said.
Coming into the game, Ross had held opposing hitters to 3-for-41 (.073) with runners in scoring position -- the best mark in the majors with a minimum of 20 at-bats. ... Rangers RHP Joakim Soria, rehabbing from Tommy John surgery, pitched a perfect inning in the rookie level Arizona League. His next scheduled outing is Friday for Triple-A Round Rock. ... Yankees INF Eduardo Nunez (strained left oblique) was set to begin a rehab assignment with Class A Tampa. ... The Yankees fell to 24-1 when scoring at least five runs. ... Rangers LHP Derek Holland (5-4, 3.43 ERA) faces RHP Phil Hughes (3-6, 5.09) in the series finale Thursday afternoon.