Nova (9-5) scattered six hits and issued one walk over nine scoreless innings. He struck out seven and tossed 73-of-108 pitches for strikes.
The shutout came less than a month after Nova's first career shutout -- an Aug. 31 three-hitter against the Baltimore Orioles.
The Yanks took a second straight from the Giants, clinching their three-game interleague series.
San Francisco starter Ryan Vogelsong (3-6) was reached for five runs on five hits in a five-inning stint.