Ishikawa put the Brewers ahead for good with a first-inning RBI groundout, and then made it 3-0 with a solo shot in the fifth.
The Brewers first baseman followed that with a three-run shot in the fourth and Rickie Weeks also homered as Milwaukee cruised to a split in their two-game series at Citi Field.
Greinke (4-1) turned in his sixth straight start without a loss, dominating the Mets on five hits. The right-hander didn't allow a walk and struck out seven while lowering his ERA to 2.88.
Mets starter Dillon Gee (2-3) was pounded for seven runs on eight hits before being yanked after 5 1/3 innings.