The slumping Granderson grounded an RBI single to cap an improbable two-run rally with two outs in the ninth inning that sent the Mets past the Miami Marlins 4-3.
''Anytime you get a chance to win and jump up and down with your teammates, it's a good thing,'' Granderson said.
Granderson was 0 for 4 when he stepped to the plate with the scoreboard showing his batting average at .130. Not quite what anyone expected for a former All-Star fresh off a $60 million, four-year contract.
''I'm not there yet, but I'm getting closer,'' Granderson said.
Cishek (1-1) had converted a team-record 33 straight save chances - the longest active streak in the majors - before Lucas Duda led off the ninth with a soft single and moved up on a sacrifice.
Left fielder Christian Yelich made a nice running catch on pinch-hitter Bobby Abreu's liner for the second out. Omar Quintanilla followed with a single down the line and Yelich slipped on the dirt as he got ready to throw home, letting Duda score standing up.
''It would've been a tough play,'' Yelich said. ''But if I had stayed on my feet, I was going home.''
Pinch-hitter Kirk Nieuwenhuis doubled to put runners at second and third. Granderson then grounded his game-winner past Jones at first base.
''I'll be up a while,'' the sidearming Cishek said. ''It's never a good feeling.''
''It's no excuse for me to come in and not get the job done,'' he said. ''I just didn't have my good command, leaving pitches down the middle.''
Granderson had a game-winning sacrifice fly in the 14th inning Sunday against Atlanta.
''He's a great hitter,'' Marlins manager Mike Redmond said. ''Just because he hasn't gotten a whole lot of hits to this point doesn't mean he's not a great hitter.''
Redmond felt confident Cishek would close out the Mets.
''He's been so good,'' Redmond said. ''I always anticipate he's going to get out of it. And tonight, he didn't.''
''You just see the momentum starting to roll their way and we couldn't stop it,'' he said.
Jeurys Familia (1-2) pitched a scoreless inning for his first big league win.
Yelich's hitting streak ended at 17 games, and the Marlins fell to 1-9 on the road.
Saltalamacchia homered to left-center off reliever Gonzalez Germen, and Jones followed with a drive off the right-field foul pole. The Mets hadn't allowed any home runs since last Saturday, a span of 57 innings.
Wheeler, a month before he turns 24, struck out 10 in six innings. He gave up four singles and walked three in six innings.
Wheeler showed off his repertoire when he fanned the side in the third, all on swinging strike three - he got Alvarez on a fastball, Yelich on a changeup and Marcell Ozuna on a curve.
A week past his 24th birthday, Alvarez gave up two runs in six innings. In his previous start, he pitched a two-hit shutout against Seattle.
Ozuna hit an RBI single in the fifth that made it 2-1.
NOTES: Marlins RHP Kevin Slowey (0-0, 4.15 ERA) is set to start Saturday night against RHP Jenrry Mejia (3-0, 1.99). ... Cishek had converted his first four save chances this season. ... In the last 11 games, no Mets starter has allowed more than three runs. ... Murphy stole third, and has been safe on his last 26 tries.