Nova went 7 1/3 inning for the Yankees, allowing one run on five hits with four walks and five strikeouts. The New York bullpen kept the Mariners scoreless until Cory Wade (5-1) served up the game-winning home run to Rodriguez.
Seattle starter Jason Vargas allowed one run on three hits, with one walk and six strikeouts over 6 2/3 innings.
Steve Delabar (1-0) got the win in relief for the Mariners, who broke a four-game losing streak.
The Yankees maintained a four-game lead over second-place the Red Sox in the American League East. Boston lost to Toronto Wednesday.