Ben Revere hit a sharp ground ball to first with two outs and the bases loaded, ending a scoring threat in the sixth.
In the bottom of the sixth, Ivan De Jesus made his first major-league home run count.
The two-run shot gave the Reds the lead for good in a 6-4 win over the Phillies on Monday night at Great American Ballpark in Cincinnati.
The Phillies took the early lead in the first as Ryan Howard doubled home Revere with two outs to open the scoring.
The Reds countered in the bottom of the first as the first three batters reached off Cole Hamels. Todd Frazier delivered an RBI single to tie the game.
Cincinnati would take the lead on a strange play in the second. Brandon Phillips worked a walk by holding up on a check swing. Thinking it was strike three, Carlos Ruiz threw to first without having a play, allowing Billy Hamilton to come speeding home from third.
Zack Cosart added an RBI double in the bottom of the third, extending the Reds lead to two.
The Phillies evened the score in the fourth on a two-run single by Ruiz.
Cincinnati regained the lead in the sixth as De Jesus belted a two-run home run. Cozart added a solo shot in the eighth to cap the Reds scoring.
Ruiz would score a run in the ninth on a wild pitch by Aroldis Chapman after working a lead-off walk.
Hamels suffered his fifth loss of the season, allowing five runs on eight hits in six innings.
The Phillies did not manage a hit against the Reds bullpen, which took over in the seventh after De Jesus' go-ahead home run.
The Phillies continue the three-game series in Cincinnati on Tuesday night against the Reds. First pitch is at 7:10 p.m.
Out of the 'Pen
At the Plate:
Kevin Durso is a contributing writer and editorial assistant for Philliedelphia. Follow him on Twitter @Kevin_Durso.