"I was looking changeup," said Brown, "It was the only fastball I had seen from him in three at-bats. So I was just trying hit something in the middle the other way and I just reacted to the ball.
"I just wanted to keep the swing short and quick and made that adjustment."
Marquis (9-3), who had won eight straight decisions over his last 11 starts, went 4 1-3 innings, giving up six runs on six hits, walking five and striking out four to take the loss.
"It was a fastball, up and out over the plate," Marquis said of the pitch Brown hit out. "It's 2-0 -- a hitter's count -- and he put the barrel on the ball."
He allowed back-to-back walks on eight pitches to Ryan Howard and Brown in the fifth inning, which led to Marquis' exit from the game and contributed to three more runs by the Phillies, who took their 6-2 lead.
Marquis, who hadn't lost a game since April 22 against Milwaukee, leads the majors in walks with 53. He has had four or more walks in 11 of his 16 starts.
The Padres have lost five of eight since a season-high seven-game win streak.
Kyle Kendrick (7-4) went eight innings for Philadelphia, allowing two runs on seven hits with six strikeouts and no walks to pick up the victory.
"It's always nice to pitch eight innings," said Kendrick. "That was a good win for us. I was throwing my cutter a lot more than usual tonight. That home run by Brown was big particularly after we gave up two and to come back and take the lead."
Brown, who walked with the bases-loaded in the fifth to drive in a run, had hit a three-run homer off Marquis in the third for a 3-2 lead.
Rollins walked to lead off the third and stole second. He went to third on a one-out single by Michael Young.
Marquis struck out Howard, but Brown hit a 2-0 pitch 411 feet into the right-center field stands. He is second in the NL in homers, one behind
The Padres had taken a 2-0 lead in the bottom of the second. Kyle Blanks singled to right and Yasmani Grandal doubled to left. Alexi Amarista's infield grounder to second scored Blanks, and Pedro Ciriaco's single to left scored Grandal.