Matt Wieters hit two doubles and drove in 1, in the third installment of a four-game series.
Guthrie (6-16) allowed one run on five hits while fanning five and walking two, earning his first win in nearly a month.
The win for the Orioles came with heavy hearts as it was learned during the game that former pitcher Mike Flanagan was found dead. He was 59.
Justin Morneau's RBI double was the sole offense for the Twins, who suffered their fourth straight defeat. Minnesota also lost right fielder Michael Cuddyer in the bottom of the first after being hit on the left wrist by a Guthrie pitch.
Kevin Slowey (0-2) didn't make it through the fifth inning, charged in the loss for seven hits and five runs.