Hernandez (10-10) limited Boston to two runs -- one earned -- on four hits and a walk in 7 1/3 innings. He also struck out nine to eclipse 1,000 for his career, becoming the third-youngest player to reach that mark.
Matt Tuiasosopo added three hits and an RBI for the Mariners, who avoided getting swept in this three-game set. Boston won Monday's series opener, then took the first game of the doubleheader, 5-3.
Tim Wakefield (3-10) took the loss after giving up four runs -- three earned -- on eight hits in 5 2/3 innings. Wakefield was named the contest's starter only a short while before Wednesday's contest, taking Jon Lester's place.
J.D. Drew homered for the Red Sox, who had a four-game win streak broken.
Russell Branyan's run-scoring groundout in the first inning gave Seattle the lead.
Hernandez set Boston down in order in the first two innings, ending the second frame by getting Adrian Beltreand Daniel Nava looking at strike three. Just before the top of the third was set to start, Beltre was thrown out for arguing balls and strikes. Red Sox manager Terry Francona came out of the dugout to state his case and was thrown out shortly thereafter.
Once the inning was actually underway, Josh Wilson hit a leadoff double and moved to third on Ichiro Suzuki's infield single. Wakefield retired the next two batters, but after Suzuki stole second, Lopez hit a two-run single to center to make it a 3-0 game.
In the bottom half, Ryan Kalish doubled with one away and moved to third when Kevin Cash reached base on Wilson's fielding error. Hernandez then threw a wild pitch to allow Kalish to score, but got out of the inning from there.
Hernandez retired the side in order in the fourth and fifth and gave up his only other run allowed when Drew hit a one-out solo shot in the sixth. That got Boston within 4-2 -- Seattle got its fourth run in the top half, on Tuiasosopo's RBI double.
The Red Sox got another scoring chance in the eighth, which pinch-hitter Bill Hall began with a double. One out later, Drew walked to chase Hernandez. However, Brandon League came in and retired the next two batters to end the threat. League stayed in for the ninth and held Boston off the scoreboard to record his fourth save.
Hernandez entered the game with 993 career strikeouts...Tuiasosopo's three hits were a career high...Lester was moved to Friday after Daisuke Matsuzaka was scratched from that start because of lower back soreness.