Barry Larkin and Ron Gant hit consecutive homers in the seventh for host Cincinnati.
Larkin's two-run homer, only his second hit in 25 at-bats, snapped a 2-2 tie with two outs in the seventh. Gant followed with his 14th homer, the Reds' third off Chris Hammond (4-2), who had allowed only four all season.
The Marlins, coming off a franchise-record 16-4 victory Friday night, managed just four hits in seven innings off Pete Schourek (5-4).
Jerome Walton homered for the Reds in the first, his fifth of the season and third game-opening homer.
Jeff Conine hit his 10th homer for Florida. Conine has been the Marlins' hottest hitter on their 12-game road trip (26-for-42, 5 HRs).