Josh Willingham gave the Twins an early lead with a leadoff home run, his first of the spring, in the second inning.
Napoli tied things up when he opened the bottom half of the frame with a homer to center field.
The Sox added three more runs in the third on Napoli's two-run double, scoring Shane Victorino and Dustin Pedroia, with Xander Bogaerts' double scoring Napoli.
Trailing, 4-1, the Twins took the lead in the seventh. With lefty Tommy Layne on the mound, Adam Brett Walker II, who is ranked Minnesotta's No. 14 prospect hit a two-run home run on the first pitch of his first plate appearance in a Grapefruit League game. Josmil Pinto gave Minnesota a lead later in the inning with a three-run shot off Layne.
Making his sixth start, Mike Pelfrey allowed four runs on five hits and three walks over four innings. The right-hander is scheduled to make his next start Friday in Cleveland, the Indians' home opener.
The Twins and Red Sox, Lee County rivals, split their Grapefruit League season series, 3-3.
Up next: With their Grapefruit League slate over, the Red Sox will head north and face the Orioles in Baltimore at 3:05 p.m. ET on Monday. Left-hander Jon Lester will make his fourth consecutive Opening Day start, the fifth-longest streak in team history, trailing only Pedro Martinez (1998-2004) and Roger Clemens (1988-94) with seven each, Dennis Eckersley (five, 1979-83), and Cy Young (five, 1904-08).
Lester, 30, is 100-56 with a 3.76 ERA in eight seasons with the Red Sox. He is 6-4 with a 2.11 ERA in 13 postseason appearances. In three Grapefruit League starts, Lester was 1-1 with a 0.71 ERA, giving up one earned run over 12 2/3 innings with three walks and 14 strikeouts. He will be opposed by Baltimore right-hander Chris Tillman.
Maureen Mullen is a contributor to MLB.com. This story was not subject to the approval of Major League Baseball or its clubs.