Niese (8-8) allowed two runs on eight hits, issuing one walk and striking out six in a 113-pitch performance.
Scott Atchison tossed a scoreless eighth and Vic Black recorded his first career save as New York rebounded from a 3-2 loss in Monday's three-game series opener.
The Mets scored all four of their runs in the second inning, highlighted by Daniel Murphy's three-run homer.
Reds starter Mike Leake (14-7) lasted just 1 2/3 innings, surrendering four runs on eight hits.
Devin Mesoraco collected the only RBI for playoff-bound Cincinnati, which fell three games behind National League Central-leading St. Louis with five games remaining.