Trailing 2-1 since the first inning, the Yankees turned it around with four runs in the eighth.
Shawn Kelley came in to pitch, prompting Yankees Manager Joe Girardi to pinch-hit Nix for Raul Ibanez. The move paid off, as Nix pounded a Kelley pitch into the left-center field gap, scoring all three runners.
Nix then came in to score on Russell Martin's single and the American League East-leading Yankees went on to take the rubber match of their three-game set.
The uprising made a winner of David Phelps (2-3) and Rafael Soriano pitched a scoreless ninth to pick up his 26th save for the Yanks.
Seattle starter Hisashi Iwakuma hurled five innings of one-run ball while Kyle Seager and Mike Carp supplied RBI in the loss.