"We always talk about this, and it's always exciting when we come here," Headley said. "I don't know why, but we just enjoy being out there. The atmosphere tonight was awesome, and it's fun to play in front of a crowd like that. We've played well here, and you just take it one game at a time and you can't think about that. When we win it's another game, and we just focus on that."
The Padres had rallied from a six-run deficit only to see the lead slip away in the bottom of the sixth inning, when Rod Barajas' RBI single gave the Pirates a one-run lead. Barajas singled to right-center off reliever Brad Brach, scoring Garrett Jones, who had drawn a base on balls and advanced to third on Pedro Alvarez's single.
But that only set the stage for Headley, who had his third multihomer game of the season and went deep from both sides of the plate for the first time in his career.
"It was a great game for Headley," manager Bud Black said. "Obviously the big blow tied the game, and the right-handed homer gave us the lead. You can't hit two bigger home runs and also [get] five RBIs when we needed [them] the most."
Brach (1-2) got the win after allowing one run on two hits over two innings.
Right-hander Edinson Volquez struggled for the Padres, charged with six runs on seven hits in 3 1/3 innings of work. He received a no-decision.
"I think it's a mechanical issue, I really do," Black said of Volquez. "I think it starts with his stride, his stride direction and stride length, which I think has gotten away from him."
Watson was saddled with the loss, falling to 5-2.
Pirates starter James McDonald had another rocky outing, allowing seven runs on seven hits in 4 1/3 innings and leaving with a no-decision.
"Put this loss on me," McDonald said. "That's unacceptable. That shouldn't happen. I let those guys down today. Nobody feels worse than me right now."
The Padres jumped out to a quick one-run lead on Alexi Amarista's leadoff home run off McDonald. It was the fourth time this season that the Padres led off the game with a home run.
McDonald has now allowed 10 first-inning runs in his last six starts.
Pittsburgh tied the score in the bottom of the second inning. With two outs, Clint Barmes singled, and he advanced to second base on a wild pitch. After McDonald drew a walk, Barmes scored on a single by Starling Marte.
With one out in the bottom of the third, Jones jumped on a 3-2 offering from Volquez, launching his 17th home run of the season into the right-field stands and staking the Pirates to a one-run lead.
In the bottom of the fourth inning, Bucs right fielder Travis Snider smacked a three-run homer, giving Pittsburgh a four-run lead. It was Snider's first home run with the Pirates since he joined them in a trade with the Blue Jays on July 31.
Alvarez continued the onslaught in the fourth, nicking reliever Alex Hinshaw for a two-run single, upping the Pirates' lead to six runs.
The Padres got to McDonald in the top of the fifth. With one out, Cameron Maybin drew a walk, then John Baker singled. Pinch-hitter Jesus Guzman doubled off the center-field wall, knocking in Maybin and Baker. Amarista then singled, plating Guzman. After Cabrera notched a base hit, Headley completed the comeback with a three-run homer that chased McDonald and tied the score at 7.
"This is something that a lot of players don't want to go through, but they have to sometimes," McDonald said. "I let the team down today, big time."
Headley's two home runs give him 17 on the season, and his five RBIs tie his game high, which he achieved on Aug. 5, 2011, in Pittsburgh. He also set a season high in RBIs, with 67.
"To be honest with you, this is probably my favorite place to play," Headley said. "The stadium is absolutely beautiful, and I've got a lot of family in the area, so it's always fun to see them, but it's just a tremendous ballpark and I've seen the ball well here."
Closer Huston Street picked up save No. 21 with a scoreless ninth inning, though he strained his left calf covering first base on the final out. The Padres are keeping their fingers crossed that it isn't a serious injury.