Vidal Nuno (1-1) came on to pitch for the Yankees starting the inning and McLouth greeted him by bashing a homer to right-center field for the decisive blow.
The blast handed the victory to closer Jim Johnson (2-4), who tossed a scoreless top of the 10th after blowing saves in each of his previous three outings, including Monday's 6-4 loss to New York.
Chris Dickerson went 3-for-4 with two solo homers for the Orioles, who evened their three-game series.
Travis Hafner drove in both Yankees runs.
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