Arrieta (1-0) was pulled after seven innings, having given up a pair of singles, walking two and striking out four.
The Orioles were up 4-0 at the time but Minnesota made it interesting with a ninth-inning, two-run home run by Josh Willingham. The Twins got the potential tying run on base before Baltimore's Jim Johnson was able to nail down the save.
Markakis spotted Arrieta a 2-0 lead in the first with a home run to left after J.J. Hardy had walked off Carl Pavano (0-1).
Markakis walked and scored on an out in the fourth and tripled in Hardy in the sixth. Markakis had two of the five hits that Pavano gave up Friday.