Two innings after he dropped a foul pop that cost the Orioles, Matt Wieters hit a fly ball of his own that scored a run to give the Orioles the lead.
Wieters came up with the bases loaded and one out in the 8th and his sac fly to right gave the O's a 4-3 lead. Adam Jones followed with an RBI single as the two-run 8th lifted the O's to a 6-3 win at Detroit.
The Orioles are now 10-2 in series openers under Buck Showalter.
The O's added to the lead on Brian Roberts' sac fly in the ninth. It scored pinch-runner Corey Patterson who ran for Jake Fox after his leadoff double.
Fox earlier hit a two-run homer in the 5th to give the O's a 3-1 lead, but in the last of the 6th, Miguel Cabrera's two-run shot, his 34th of the year, tied the game 3-3.
The runner that scored on the homer, Johnny Damon, drew a walk after Wieters dropped his foul pop for an error.
But the O's regained the lead and made it stand up to win the series opener in Detroit and improve to 3-1 on a six-game road trip.
Kevin Millwood did not get a decision, giving up three runs (two earned) and eight hits over six innings, throwing 106 pitches.
David Hernandez, in his first big league outing since August 4th, gave up a leadoff triple, but no runs in the last of the seventh as he got two strikeouts and a popup to strand the runner.
Jim Johnson pitched a scoreless 8th and Koji Uehara a 1-2-3, 9th for his 8th save.
The Orioles have won five of the last six and nine of their past 13 games and are 22-14 under Buck Showalter.
They knocked off a Tigers team that falls to 46-26 at home and has lost just three of its last 12 home games.
The Orioles ended a five-game losing streak at Comerica Park.
In game two of this series on Saturday night, it's Jeremy Guthrie (9-13, 3.89) vs. Max Scherzer (10-9, 3.51).
In the Carolina League playoffs tonight, Frederick was held to four hits in a 7-1 loss at Potomac. The Nationals take a 2-1 lead in the best of five series.
Zach Clark took the loss, allowing three runs over three innings and the Keys offense was held to four singles. Game four is Saturday night at Potomac.