Santana (5-3) followed R.A. Dickey's one-hit shutout on Monday with another dominating performance for New York, scattering four hits while issuing two walks and striking out five.
The left-hander, who pitched the Mets' first-ever no-hitter June 1, won for the fourth time in five starts as New York clinched a series win.
Lucas Duda went 2-for-4 with a two-run homer and Jordany Valdespin contributed a two-run single .
Orioles starter Tommy Hunter (3-4) was tagged for all five runs on seven hits in a 6 1/3-inning effort.
Celebrity Families of 2014 [PHOTOS]