Victorino snapped an 0-for-11 slump with his homer off right-hander Homer Bailey (7-6), improving the Phillies to 4-1 against Cincinnati this season.
Hamels held the Reds to two hits - one a misplayed fly ball - in six innings. Antonio Bastardo (6-0) fanned three in his one inning of relief. Dave Sappelt's infield single drove in a run in the eighth, cutting it to 3-2
Ryan Madson gave up a hit in the ninth before finishing it off for his 24th save in 26 chances.
The Phillies were coming off two unplanned days off because of Hurricane Irene. The rainouts left them with a formidable schedule the rest of the way - 33 games in 31 days.
Nice way to get it started.
Hamels was sharp in his first start since Aug. 12, a break caused by an inflamed pitching shoulder. He had a good matchup for his return - the left-hander has enjoyed some of his best moments against the Reds.
Hamels fanned seven without walking a batter, throwing 50 strikes out of 76 pitches before leaving with the score tied at 1. He remained 8-0 in his career against the Reds, including a shutout at Great American Ball Park that completed the Phillies' playoff sweep last season.
Bailey fanned a season-high nine batters, but made one bad pitch out of 100 that turned the game. Cincinnati lost for only the second time in its last eight games.
Misplays in the outfield set up the first two runs.
Brandon Phillips extended his hitting streak to 12 games - longest by a Red this season - when Hunter Pence slipped on the warning track while trying to catch his fly ball. Pence's feet went out from under him, allowing the ball to drop just out of his reach for a triple. Phillips scored on Joey Votto's groundout.
Sappelt, a rookie, had a bad moment in left field in the fifth. He initially broke back on Wilson Valdez's line drive, then came in, dived and missed the ball, letting it skip past him for an RBI double that tied it at 1.
Hamels pitched out of a threat in the sixth, when the Reds got a runner to third with two outs. He fanned Sappelt for the third time to end the inning.
The game marked Yonder Alonso's professional debut at third base for the Reds, who are trying to find a position for their former first-round draft pick. Alonso didn't get any balls hit his way. He grounded out and struck out three times, including in the ninth against Madson.
Notes: The Phillies have gone 33 road games without consecutive losses, the best such streak in club history. ... Phillies manager Charlie Manuel sees one area the Phillies could improve through trade in the next two days. "We could definitely use some players on our bench," Manuel said. "We've been short." Teams must complete trades by the end of August for the player to be eligible for the postseason. ... RHP Roy Halladay starts the second game of the series against Cincinnati, the team he no-hit during the playoffs last season. The Reds go with Bronson Arroyo, who is 1-6 career against the Phillies with a 7.13 ERA.