"He was throwing me around like a rag doll," Mauer said of being picked up the big slugger Sano. "I knew you got to kind of keep an eye out for him. It was fun. It's fun to get out there and jump around with the fellas."
Mauer's blast off reliever Matt Barnes (3-1) was the first career walk-off home run in 14 major league seasons and just the fourth walk-off plate appearance of his career. Mauer added an RBI single as Minnesota won for the seventh time in its past nine games.
Boston reliever Robby Scott retired Eddie Rosario -- who had two hits to extend his hitting streak to a career-best 15 games -- and Barnes got pinch-hitter Kennys Vargas to ground out in the ninth. Down to his last strike, Mauer drove a pitch deep to the bullpens in left-center field through the wind on a breezy night at Target Field.
"Wind was kind of crazy there," Mauer said. "I knew I hit it about as good as I could. So if that didn't go out, then I'd be pretty upset. It felt good off the bat and I was just hoping it would go."
Brandon Kintzler (1-0) suffered his first blown save in eight chances this season as Boston's Chris Young hit a pinch-hit RBI single in the top of the ninth.
Mitch Moreland and Josh Rutledge started the inning with infield singles. Jackie Bradley Jr. grounded out before Young hit a hard grounder right down the third-base line to tie the game.
"Just took a chance with (Young), fresh set of legs and maybe some bat speed," Red Sox manager John Farrell said. "It paid off. Unfortunately, they answer right in the bottom half of the inning."
Phil Hughes had his best start of the season for Minnesota, with one run allowed on six hits in 6 2/3 innings. Sano continued his strong play with two hits, a walk, run scored and RBI.
Hughes is dealing with diminished velocity this season after recovering from surgery to relieve thoracic outlet syndrome last year. But the right-hander kept Boston off-balance and got out of some trouble in the early innings.
"First-pitch strikes and I didn't want to just throw it over the plate, necessarily," Hughes said. "I was able to hit some spots and get ahead in the count to a lot of these guys, and was also able to get some quick-count outs, which helped my pitch count later on down the line."
Eduardo Rodriguez pitched six innings for Boston, giving up three runs on seven hits. He struck out six.
Minnesota got to Rodriguez early with two runs in the first inning.
Mauer was hit by a pitch and Sano sent a towering shot to right field. Boston's Mookie Betts got turned around and couldn't catch the ball, which hit off the wall and rolled into shallow right field. Sano went into third with a triple and Mauer scored.
"Most people take that swing and it's a pop-up to the second baseman," Twins manager Paul Molitor said. "It looks like it gets way in on him and it's an awkward swing, and the next thing it's off the wall. A lot of strength there."
Sano scored when Robbie Grossman's liner went off third baseman Rutledge's glove into left field.
Boston's Andrew Benintendi followed in the third inning with a solo homer, his fourth of the season.
"We know that this is a lineup that's going to have to produce top to bottom," Farrell said. "It's not going to revolve around one big hitter in the middle of the lineup -- we need contributions up and down and bunch our hits together. Right now that combination has not been there."
NOTES: Minnesota 2B Brian Dozier left the game in the ninth inning with a sprained ankle. Dozier suffered the injury earlier in the game and played through it, but couldn't continue and was pinch-hit for in the ninth. Manager Paul Molitor said Dozier is considered day to day. ... The Twins selected the contract of RHP Drew Rucinski from Triple-A Rochester and designated outfielder Danny Santana for assignment to make room on the 40-man roster. The team also activated IF Ehire Adrianza from the disabled list to fill the spot vacated when RHP Kyle Gibson was optioned following Thursday's game. Adrianza has missed the entire season with a right oblique strain. ... Boston recalled IF Deven Marrero and optioned RHP Brandon Workman to Triple-A Pawtucket. ... Red Sox manager John Farrell said Brock Holt (vertigo) would play DH tomorrow during a rehab appearance. Farrell also said 3B Pablo Sandoval (right knee sprain) is improving and could hit off a tee on Saturday. ... Minnesota CF Byron Buxton was held out on Friday. Molitor said Buxton is sore and dealing with some headaches but the team believes there is no concussion. Buxton passed a concussion test on Thursday after leaving the game early when he collided with the outfield wall. ... Twins 3B Miguel Sano had a hearing for his appeal of a one-game suspension for shoving Detroit C James McCann. Molitor said the team expects to hear the verdict on Monday or Tuesday.