Ryan Flaherty also homered and had a career-high three hits for the Orioles, who never trailed but had to withstand four homers by Seattle.
McLouth connected off Brandon Maurer to make it 11-6 in the sixth, and that was enough offense to fend off the Mariners, who closed the gap in the eighth with solo shots from Kendrys Morales and Michael Morse.
Jim Johnson worked the ninth to earn his 38th save and secure the victory for Chris Tillman (14-3).
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