Justin Turner knocked in the game-winning run 4 victory over the Cubs in the game series.
Manny Acosta (3-1) blew the save in the top of the ninth but was given the win.
Turner had three hits and two RBI, and Jason Bay doubled twice and knocked in a run for New York, which was coming off a double-header sweep at the hands of the Braves on Thursday.
Sean Marshall (6-6) allowed the game-deciding run to take the loss.
Carlos Pena smacked a two-run homer as Chicago dropped its fifth game in eight tries.
Mike Pelfrey went 6 2/3 innings, allowing three runs on six hits and three walks in the start for the Mets, and Casey Coleman allowed four runs on eight hits through five innings for the Cubs. He struck out five and did not walk a batter.
"I was up [in the zone] a little bit," Coleman said. "They were more aggressive."
Nick Evans greeted Marshall in the bottom of the ninth with a base hit to center field. Josh Thole then laid down a sacrifice bunt to move pinch-runner Jason Pridie to second. After pinch-hitter Ruben Tejada lined out to second, Jose Reyes was intentionally walked to get to Turner, who belted the second pitch he saw over the head of Marlon Byrd in center field to end the game.
The Cubs left the bases loaded in the first inning, but were able to break through in the third. Aramis Ramirez hit a two-out double before Pena hammered a ball into the seats in center field to give Chicago a 2-0 lead.
Byrd singled to start the fourth inning and was followed by Bryan LaHair's first career triple off the base of the wall in right. Two batters later, Coleman lifted a ball to left field. Bay made the grab and fired the ball home, catching LaHair at the plate for the inning-ending double play.
In the home half of the fourth, back-to-back base hits by Turner and Lucas Duda put runners on the corners. David Wright followed with a grounder to short, allowing Turner to cross the plate as Wright beat out the potential double play at first.
Wright moved to second on Angel Pagan's single and came home on Bay's double down the third-base line. Evans then hit a hard grounder to third that deflected off of Ramirez's glove, allowing Pagan to score and tying the game at three.
"We needed that, especially down in a 3-0 hole," Pelfrey said.
Reyes hit a ground-rule double with one out in the fifth, and Turner followed by slapping a double to right field to give the Mets their first lead of the game.
Acosta started the ninth for New York trying for the save. After striking out Tony Campana, Geovany Soto walked and was replaced by pinch-runner Lou Montanez. Montanez was almost doubled off at first after he wandered too far off the bag on a soft liner to second by pinch-hitter Reed Johnson, but consecutive singles by Starlin Castro and Darwin Barney scored Montanez and knotted the game at four.
Reyes extended his hit streak to 12 games...Castro extended his hit streak to 10 games and has now reached base safely in a career-high 22 straight games...Coleman has not recorded a win since May 19...The Mets and Cubs have met 692 times since 1962 and the all-time series is tied 345-345 with two ties.