Markakis went 3-for-5 with a home run and Vladimir Guerrero knocked in a pair for Baltimore, which avoided three-game sweep at the hands of the Tigers picked up just its second win in eight tries.
Jo-Jo Reyes (6-9) pitched the O's to the victory, limiting Detroit to one run on four hits over six innings.
The Tigers' Doug Fister (4-13) absorbed the defeat after yielding eight runs (six earned) on 12 hits before being yanked after 5 2/3 innings.
Ramon Santiago contributed two RBI, including a solo homer, and Austin Jackson chipped in with three hits and a run batted in as American League Central-leading Detroit saw its three-game winning streak snapped.
Notable deaths of 2014 [PHOTOS]