Wheeler (5-2) surrendered six hits, didn't issue a walk and struck out four, placing 68-of-106 pitches for strikes.
Scott Rice, Carlos Torres and Pedro Feliciano combined for 1 2/3 innings scoreless innings and LaTroy Hawkins earned his third save as the Mets rebounded from a 5-4 loss in Friday's three-game series opener.
Flores provided an RBI single after a Juan Lagares solo homer in the fourth inning and added a two-run single in the eighth for New York.
Brandon McCarthy (2-6) took the loss, yielding two runs on six hits over seven full innings.
Aaron Hill went 2-for-4 with an RBI for the D-backs, who fell 6 1/2 games behind the National League West-leading Los Angeles Dodgers.