Bengie Molina and Aaron Rowand hit consecutive home runs, and Jose Castillo also connected to help the Giants win their third consecutive game.
Zito (1-8) allowed one run and three hits in 6 1-3 innings. He struck out five and walked four for his first victory since Sept. 30, 2007, when he defeated the Los Angeles Dodgers in San Francisco's season finale.
Making his 10th start this year, the left-hander avoided becoming the first starter in franchise history to begin a season 0-9. The 2002 AL Cy Young Award winner with Oakland, Zito has been a bust in San Francisco since signing a $126 million, seven-year contract before last season.
Rowand drove in three runs, and Molina and Rich Aurilia each had two RBI to lead the Giants.
Dan Uggla hit his 15th homer for Florida. The NL East-leading Marlins were coming off a three-game sweep of the Arizona Diamondbacks, who lead the NL West.
Molina and Rowand homered in the fourth, giving the Giants a 7-1 lead and chasing Florida starter Scott Olsen after 3 1-3 innings. Olsen (4-2) allowed seven runs and eight hits, struck out two and walked three in his shortest outing of the season.
The Marlins also lost starting right fielder Brett Carroll after Rowand's home run. Carroll sprained his right shoulder after hitting the wall while chasing Rowand's shot. Jacque Jones, who joined the club Friday, replaced Carroll.
Castillo hit a solo shot in the eighth.
Rowand's RBI single and Aurilia's two-run double in the third increased the Giants' lead to 5-1.
The Giants got to Olsen quickly with a two-run first. Molina's run-scoring single and Rowand's sacrifice fly gave San Francisco the early lead.
Uggla drove in both runs for the Marlins, a two-out RBI double in the first and his home run in the ninth.
