Boston took the lead 1-o in the second inning, before Justin Morneau hit a home run for the Twins to lead off the fourth inning with a drive over the right field wall at Hammond Stadium to tie the score.
The Red Sox added another run in the fifth to go ahead 2-1 and secure the win.
Morneau, who left the club after the game to join Canada in the World Baseball Classic, is hitting .471 this spring.
Joe Mauer hit 1 for 3 for the Twins and caught the first five innings. Mauer will leave the team Sunday to join Team USA for the WBC.
Three other Twins -- pitcher Samuel Dedundo, infielder Jamey Carroll and reliever Glen Perkins -- will also take part in the WBC. Carroll and Perkins will play for Team USA, while Deduno will go to the mound for the Dominican Republic.
With the loss, the Twins dropped to 5-3 in spring training play. The team will take on the Tampa Bay Rays Sunday in Port Charlotte.