Phil Hughes (5-5) broke a personal three-game winless streak, allowing one run on five hits over six innings as New York extended its lead in the American League East to four games over idle second-place Boston.
Seattle's Felix Hernandez (14-12) lost to the Yankees for the first time in his career after going 5-0 against them in six previous starts.
The reigning AL Cy Young Award winner was rocked for six runs on nine hits over six innings.
Miguel Olivo launched a two-run homer for the Mariners.
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