The Phillies' second inning started with Ryan Howard's broken-bat roller against the infield shift into left field. Two more hits followed, including Domonic Brown's RBI single up the middle. On a 2-2 slider, Erik Kratz hit a three-run home run to left-center field to give the Phillies a quick 4-0 lead.
In the third, Leake issued a leadoff walk before Chase Utley lifted the first pitch to straightaway center field for a two-run homer and a 6-0 advantage. Leake was lifted after a one-out double by John Mayberry Jr.
"I had trouble keeping the ball where I wanted it," said Leake, who was roughed up for six earned runs and six hits with two home runs in only 2 1/3 innings.
In five starts lifetime vs. the Phillies, Leake is 0-3 with a 9.33 ERA (28 earned runs over 27 innings). On Aug. 20 at Philadelphia, he gave up a career-high seven runs over 4 1/3 innings.
"They've got a good plan and make me work," Leake said. "They know what they're doing. They're all a bunch of great veteran hitters. I just haven't been able to figure them out yet."
Leake, who was 3-1 in five starts last month -- including wins in his last two starts -- fell to 7-9 with a 4.73 ERA. As the Reds consider their options for the postseason roster, Leake could find himself on the outside of the rotation -- especially in the National League Division Series.
With only 24 games remaining on the season, the Reds still have an 8 1/2-game lead over the Cardinals, who also lost on Wednesday. The magic number -- the combination of Cincinnati wins and St. Louis losses -- to clinch the NL Central is 17.
The Reds dropped two of three in this set and four of seven in the season series. They haven't beaten the Phillies in a season series since 2003.
"It was good that we got a lead today. We jumped out and got ahead of them," Phillies manager Charlie Manuel said.
Despite being 66-71, the Phillies have improved dramatically since getting Howard and Utley back from injuries, and they have been a good playoff test for the Reds. It's only the third time since the All-Star break that the Reds have lost a series. They're 11-3-2 in second-half series.
After Thursday's off-day, baseball's worst team comes to town, when the Astros visit for three games.
"We'll enjoy that day off, take advantage of it and come back strong on Friday," manager Dusty Baker said.
Cincinnati's bullpen contained the damage after Leake departed, as Alfredo Simon, Sam LeCure, Sean Marshall and debuting rookie Pedro Villarreal combined to retire Philadelphia's final 17 batters in a row.
However, Phillies ace Roy Halladay is now 110-0 over his career in games that he's given a lead of four or more runs. Halladay cruised, allowing one run and eight hits over 7 1/3 innings, with one walk and five strikeouts.
In the bottom of the fourth inning, hot-hitting Jay Bruce lined a two-out RBI double to right field that scored Chris Heisey and put the Reds on the scoreboard against Halladay.
Bruce returned in the ninth inning to slug a leadoff homer on a 1-1 pitch from Jonathan Papelbon. The outfielder tied a career best with homers in four straight games, and five of his last six.