Wieters became the fourth Baltimore catcher to reach 700 games behind the plate and went 3-for-4 with two RBIs. He tied a career high with three extra-base hits, two doubles and the homer, and knocked in two runs.
His first double, which came in the fourth, broke a 2-2 tie and gave the Orioles (24-14) the lead for good. Wieters later doubled and scored on a Jonathan Schoop sacrifice fly and has gone 6-for-15 on the current homestand.
"I'm seeing the ball good," Wieters said. "Early in the year, I was just going up there pre-swinging and pre-taking. Now, going up and being able to recognize pitches, any time you feel good at the plate, you're seeing the ball well."
The Orioles also got a lift from another solid Tillman start. He's now won each of his last five starts, improving to 6-1 overall, and allowed two runs on four hits in 6 1/3 innings.
Tillman again mixed his pitches well, which has been his strong point this year, and kept Seattle (22-17) quiet.
He gave up a solo homer to Leonys Martin in the third and battled some control issues in the third and fourth but recovered to finish strongly and improved to 7-0 vs. the team that drafted him 10 years ago and traded him to Baltimore in 2008.
"I felt good physically; the pitches kind of came along as the game went on," Tillman said. "I felt good with all my pitches. I'm happy with it."
Orioles manager Buck Showalter has been pleased with the way Tillman's thrown all season and liked what he saw in this game.
"He was solid again," Showalter said. "He was good. (He) carried stuff the whole outing."
Brad Brach threw one inning before closer Zach Britton entered with the bases loaded and one out in the eighth and retired the final two batters. The left-hander then finished off his 11th save in the ninth.
Baltimore's power helped its pitchers once again. Trumbo snapped an 0-for-7 skid when he homered to start the second. Wieters followed with his solo homer.
Seattle starter Taijuan Walker (2-3) gave up four runs on five hits, including the two homers, in his five innings and said he just never got it all together.
"My rhythm was a little off," Walker said. "I didn't (throw) my best. I didn't really locate too well, kind of got behind. I was just throwing too much off-speed and not going to my strength, (my) fastball and change-up."
The Mariners did not help by missing on several scoring chances, going 1-for-12 with runners in scoring position and stranding nine.
"We battled, we had chances," Seattle manager Scott Servais said. "We needed to come up with the big hit and didn't quite get it to get back in the game."
The Orioles hit back-to-back homers for the seventh time this season when Trumbo and Wieters banged their solo shots in the second for a 2-0 lead.
Seattle answered when Martin led off the third with a homer that cut the Baltimore lead in half. The Mariners then tied it in the fourth when Nelson Cruz led off with a double and later scored on Chris Iannetta's sacrifice fly.
Trumbo and Wieters combined for more Baltimore offense in the fourth. Wieters doubled to center to bring in Trumbo, who had reached on a one-out single, giving the Orioles a 3-2 lead.
Baltimore made it 4-2 in the fifth. Trumbo was up with the bases loaded when Walker's wild pitch led Hyun Soo Kim score from third with two outs.
NOTES: Orioles manager Buck Showalter said RHP Yovani Gallardo (biceps tendinitis) threw from 120 feet and will do the same Thursday. If all goes well, Gallardo would then throw a bullpen session Sunday in Anaheim and again two days later in Houston. After that, he would throw a simulated game on May 27. ... RHP Hunter Harvey, one of the Orioles' top prospects, is scheduled to start a throwing program on May 24. He has had a number of injury issues in the last few seasons, the latest being sports hernia surgery this spring. ... The Mariners will receive a player to be named or cash from San Diego after they declined to take back OF Jabari Blash, a Rule 5 draft pick just designated for assignment. ... There is something about Oriole Park that brings out the best in 2B Robinson Cano. Heading into Wednesday night's game, Cano had a .367 average in Baltimore with 15 homers and 46 RBIs in 83 career games.