But the O's came right back against Brett Myers (2-2). Mark Reynolds drew a one-out walk and McLouth followed by blasting a pitch over the right field stands for the decisive blow.
He finished with three RBI and Lew Ford also homered for the American League wild card-contending Orioles, who won a one-run decision for a 13th straight time.
Pedro Strop (5-2) was credited with the decision despite yielding the go-ahead tally and Jim Johnson racked up his MLB-best 40th save for the victors.
Youkilis belted a two-run homer for AL Central-leading Chicago, which saw its six-game winning streak snapped.