Joe Mauer gave the Twins a 2-1 lead with a two-run homer in the sixth, but Scott answered with a two-run drive in the bottom half off rookie Anthony Slama (0-1) to give Baltimore its second win in eight games since the All-Star break.
Miguel Tejada had two hits and scored twice for the Orioles, now 3-50 when scoring fewer than four runs.
Baltimore second baseman Brian Roberts was activated from the 60-day disabled list before the game and went 0 for 4 in his first game since April 9. He had been sidelined with back and abdomen injuries.
Guthrie (4-10) gave up six hits, struck out six and hit a batter with a pitch. The right-hander was 0-6 in his last nine starts and had gone six straight outings without pitching seven innings.
The Twins put runners at the corners with two outs in the eighth against Will Ohman before David Hernandez got Michael Cuddyer to fly out to Adam Jones at the center-field wall.
Alfredo Simon worked the ninth for his 14th save.
Twins second baseman Orlando Hudson left in the third inning with a muscle strain near his right rib cage. He was replaced by Alexi Casilla, who singled before Mauer hit his fifth homer of the season.
Leaving the bullpen to make his first start of the season, Minnesota's Brian Duensing allowed one run and four hits in five innings.
The Orioles used singles by Tejada, Scott and Jones to go up 1-0 in the first inning. Jones' RBI hit ended the team's 0-for-15 skid with runners in scoring position.
Ty Wigginton hit his first triple since August 2008 with two outs in the third, but was stranded when Scott struck out.
NOTES: Twins 3B Nick Punto made an outstanding play in the sixth, diving to the line to snare a grounder by Jones before making a perfect throw from his knees to get the out. ... Wigginton received a three-game suspension and a fine for making contact with umpire Gary Darling on Thursday night. He appealed the punishment, which enabled him to play Friday. ... The Twins held the opposition scoreless for 19 innings before the Orioles scored in the first. Minnesota had two straight shutouts and has had three in a row only once — July 5-7, 2004. ... Orioles RF Nick Markakis was given the night off. It was the second game he missed this season — the other came on the night his wife gave birth to a baby boy. ... Twins RF Jason Kubel snapped an 0-for-14 drought with a sixth-inning single.