Markakis collected RBI singles in the third and fourth innings to help the O's overcome an early deficit and Jeremy Guthrie pitched six-plus strong innings as Baltimore won the make-up game of a Friday night rain-out at Target Field.
Guthrie (1-4) got his first win of the year, yielding three runs on five hits and a walk over 6 2/3 innings while fanning five.
Julio Lugo collected three hits and an RBI while Cesar Izturis scored three times to deal the Twins their first back-to-back losses in their new ball park.
Justin Morneau connected for a two-run home run in the first inning while Michael Cuddyer added a solo shot in Minnesota's loss. Starter Francisco Liriano (4-1) allowed five runs on 10 hits with a walk in six innings of work.