McCullers had not pitched since June 8th due to a sore back, but didn't allow a hit to the Mariners until the 5th inning.
The Astros went 6-1 on this swing and improved to a major league-best 29-9 on the road.
The Astros have an off day tomorrow, then return home to open a four game home series against the A's next week.
Houston hit three home runs and used five pitchers to keep the Seattle bats silent as the Astros took the rubber game of the three-game series 8-2 Sunday at Safeco Field.
"I feel good", McCullers said according to MLB.com. "I just tried to get ahead and stay ahead". "And, it's a positive thing that my arm was feeling good".
Springer led off the inning with his 22nd home run, a 456-foot blast to straightaway center field that hit almost halfway up the black batter's eye beyond the fence. RHP Mike Fiers (5-2, 3.81 ERA) starts against LHP Sean Manaea (6-4, 4.05 ERA).
"I didn't think it had enough to get out, honesty", Reddick said. The Mariners actually had a chance to win the game in the ninth inning, when a base hit and three walks in a row brought in a run and loaded the bases for Carlos Ruiz. Left-hander James Paxton (5-2, 3.39 ERA) goes for the Mariners.
In the seventh, Springer singled with one out and Reddick reached on catcher's interference. McCann followed with a drive to right that Mitch Haniger briefly had in his glove on the diving attempt as he raced toward the line, but the ball popped free as he hit the ground.
"I was going insane when I was on the DL".
Hernandez struck out eight, and Yovani Gallardo picked up the save pitching the final three innings in his first relief appearance since 2007. Nelson Cruz led off with an infield single - the M's first of the night - and Kyle Seager ripped a double off the wall in center. Cruz was caught midway between third base and the plate, caught in a rundown by McCann for the second out as Seager advanced to third.
"It was nice to see him come out pretty hot", Astros manager A.J. Hinch said. He was mid-90s from the very beginning and had a really good breaking ball.
McCullers cruised in his first start off the DL until running into a little trouble in the fifth. Even if the Mariners should suffer more injuries to their pitching staff in the months to come, they look to have several serviceable spot starters in Gaviglio, recent call-up Andrew Moore, and Christian Bergman. Astros 1B Marwin Gonzalez was a late scratch for Saturday's game, suffering from what the team called tightness in his right oblique.
And it was easily the most competitive of the three series played this season.
PLUS: Except for one hard fourth inning, left-hander Ariel Miranda (seven-plus innings, four runs) continues to give the team great pitching - and eat innings. Peacock tweeted. Peacock was placed on the paternity list and RHP Jordan Jankowski was recalled from Triple-A Fresno.
George Springer and Yuli Gurriel both homered in a four-run fourth inning against Seattle starter Ariel Miranda (6-4) as the Astros erased a 2-0 deficit.
A day after climbing over.500 for the first time this season, the Mariners continued their June surge with their sixth straight win thanks to an offense that knocked out Houston starter Joe Musgrove (4-7) early and got a strong performance from Hernandez.