Matt Wieters went deep and Adam Jones scored four times for the Orioles, who moved within a half-game of the first-place New York Yankees. Baltimore also opened a three-game cushion over the Los Angeles Angels for the second AL wild-card spot.
Chris Tillman (8-2) allowed one run and three hits over six innings, supported by Baltimore's 15 hits. He struck out four and walked none.
Jones and Tillman were two of the five players Seattle sent to the Orioles in a lopsided trade for left-hander Erik Bedard in February 2008. The right-hander is 4-0 with a 0.98 ERA in four career starts against his former club. Against everyone else, he is 11-17 with a 5.44 ERA.
McLouth, Wieters and Jones each had three hits. Jones' four runs set a season high for an Orioles player.
The Mariners scored all their runs on homers. Michael Saunders hit an opposite-field shot, his 16th, to left in the second off Tillman. Eric Thames hit his eighth off Zach Phillips in the eighth and John Jaso had a two-run drive, his ninth, off Luis Ayala in the ninth.
The Orioles jumped on starter Hector Noesi (2-12) from the first batter and didn't let up until they chased him after just 1 1-3 innings.
McLouth opened the game with a home run into the right-field seats on an 0-2 pitch. Mark Reynolds and Manny Machado each had an RBI single later in the first.
J.J. Hardy and Reynolds each had a run-scoring double in a four-run second, and Jones added an RBI single. Another run scored on an error for a 7-0 lead.
Noesi gave up eight hits and six earned runs in his 54-pitch outing. He walked two and struck out one.
Wieters hit a two-run homer to center in the fourth on the first pitch from Oliver Perez. It was his 22nd, tying his career high.
Endy Chavez finished the Orioles' scoring with an RBI single in the sixth.
The Orioles have won six of seven meetings with the Mariners this season.
NOTES: Baltimore manager Buck Showalter said he's "pleasantly surprised" that OF Nick Markakis does not need more surgery on his injured right thumb. Markakis was hurt Sept. 8 and was given a six-week timetable for a return. It's unlikely he'll be available unless the club advances well into the playoffs. ... Orioles RHP Jason Hammel, who came out of his start last Tuesday with a knee issue, is progressing slowly, according to Showalter. It's uncertain when he will start again. ... Baltimore RHP Miguel Gonzalez likely will start Friday in Boston. ... Mariners manager Eric Wedge started his regulars. "We are going to put out our best lineup," he said. He added that his players are doing more than just showing up. "No one is looking at the finish line right now," he said. "I don't sense that at all. They're all focused on today."