Nick Swisher and pinch-hitter Hideki Matsui also homered for the Yankees, and Johnny Damon hit a tiebreaking, two-run double. Jayson Werth connected twice and Carlos Ruiz had one homer for the defending champion Phillies
"This was my first time coming to this ballpark. It just seems like you're going to have a slugfest a lot," Swisher said. "It was a great day for us."
Rodriguez's shot in the fourth inning was originally called a double. It was his first hit in the Series, and became a two-run homer after umpires reversed the call and correctly ruled it hit a camera above the right-field wall.
"It was a big hit. I think it woke our offense up a little bit," Rodriguez said.
After pitching dominated the first two games in the Bronx, the Yankees and Phillies showed their muscle, combining for six home runs.
Rain affected the Series schedule in Philadelphia for the second consecutive year, delaying the start by 1 hour, 20 minutes. Once they hit the field in front of their boisterous fans, the Phillies took a 3-0 lead - but it was squandered by a struggling Cole Hamels.
Game 4 is Sunday. Joe Blanton pitches against Yankees ace CC Sabathia, who goes on three days' rest for the second time this postseason.
Pettitte settled down after a shaky start and even helped himself at the plate with a tying single. His six-inning outing was enough to earn his 17th postseason win, extending his major league record.
"He closed off our left-handed hitters," Philadelphia manager Charlie Manuel said.
Ruiz homered in the ninth off Phil Hughes. Mariano Rivera finished up at 12:42 a.m. local time in a non-save situation.
"It was an absolute grind tonight, that's for sure," Pettitte said. "I can't remember winning a game where I've struggled like I did tonight. So it's very gratifying."
With the Yankees down three runs, Mark Teixeira walked in the fourth and Rodriguez hit an opposite-field drive deep into the right-field corner. He cruised into second base with an apparent double after the ball ricocheted back onto the field.
Video replays, however, showed the ball struck the lens of a television camera positioned just above the fence at the 330-foot sign. New York manager Joe Girardi came out to talk with right-field umpire Jeff Nelson as Phillies pitching coach Rich Dubee visited the mound.
The signal: home run.
(Left: The Phillies' Cole Hamels waits while umpires discuss a hit to right field by Yankee Alex Rodriguez during the fourth inning of Game 3 of the World Series Saturday. The hit, originally called a double, was changed to a two-run home run.)
"I couldn't see it," A-Rod said. "When we got the call I was happy."
Rodriguez's first hit in nine World Series at-bats was his sixth homer this postseason, tying Bernie Williams' club record from 1996. It also was the 17th postseason homer this year for the Yankees, setting a franchise mark.
"It was much more like myself," Rodriguez said. "Tonight I was a lot more disciplined, and better results."
New York kept hitting in the fifth and chased Hamels. Swisher opened with a double and slid home with the tying run when Pettitte looped a one-out single to center on a first-pitch breaking ball.
Jeter fisted a soft single and Damon cracked a two-run double to right-center for a 5-3 lead. Hamels was lifted after another walk to Teixeira and walked off the mound to a mix of boos and cheers.
Swisher homered off rookie J.A. Happ in the sixth and took a long look at his solo shot to left, which made it 6-3.
Werth answered leading off the bottom half with a mammoth drive off the facing of the second deck in left. After connecting, he slammed his bat to the ground and glared into the Philadelphia dugout as if to urge on his teammates.
It was Werth's seventh home run this postseason, one short of the major league record held by Carlos Beltran (2004) and Barry Bonds (2002).
Jorge Posada's RBI single off Chad Durbin in the seventh gave New York a three-run cushion, and Matsui added a solo shot as a pinch-hitter in the eighth.
Matsui was on the bench because World Series rules don't permit a DH in National League parks.
Pettitte fell behind 3-0 in the second inning. Werth reached down for a breaking ball and hit a leadoff homer to left, setting off fireworks and lighting up the Liberty Bell in right-center field.
Pedro Feliz doubled off the right-field wall, Ruiz walked and Hamels' bunt single loaded the bases. Jimmy Rollins walked to force in a run and Shane Victorino added a sacrifice fly.
Pettitte avoided further damage by striking out Chase Utley, then settled in and held Philadelphia in check.
The grounds crew was still drying puddles on the warning track as the Phillies took the field.
Last season, Game 5 of the World Series between the Phillies and Tampa Bay was suspended for two days because of rain. Once it resumed - in the sixth inning - the Phillies went on to a 4-3 victory that clinched the championship.
By AP Baseball Writer Mike Fitzpatrick