Hernandez (1-0), who signed a seven-year, $175 million contract with the Mariners in February, dominated the Athletics on three hits, yielding only one walk in the 109-pitch performance.
The right-handed ace retired the first 10 batters he faced and allowed only one runner to reach as far as third base.
Tom Wilhelmsen notched a scoreless ninth for the save as the M's took the first of a four-game road series.
Franklin Gutierrez provided the game's only offense with a two-run single in the fifth inning.
Oakland's Brett Anderson (0-1) absorbed the loss, surrendering two runs on four hits in a seven-inning effort.