Jhonny Peralta added two home runs for Cleveland.
"It was emotional at first," said Lofton, who was traded from Texas for minor league catcher Max Ramirez earlier in the day. "The fans were cheering and I was trying to calm myself down the first time up. I didn't know what to expect and it was nice to go out there and show the fans I have a little bit left."
He struck out in his first at-bat, but provided a spark during the Indians' six-run third.
After Josh Barfield reached on an error and Sizemore walked, Lofton dropped a bunt that bounced off the plate, and by the time Bonser grabbed it, he had no chance of throwing out the speedster.
In other AL games Friday, it was New York 8, Baltimore 7 in the completion of a suspended game; Baltimore 4, New York 2; Boston 7, Tampa Bay 1; Kansas City 6, Texas 1; Chicago 4, Toronto 3; Los Angeles 11, Detroit 6; and Seattle 7, Oakland 1.
Lofton, a lifetime leadoff hitter and center fielder, batted second and played left. He finished 3-for-5 with an RBI in his first game for Cleveland since leaving after the Indians were eliminated in the 2001 playoffs.
That was the last time they made the postseason, and the Indians are hoping Lofton can help them get back.
"We got a shot in the arm," pitcher Paul Byrd said of Lofton's arrival. "We got somebody who knows how to win in playoff situations, a gamer. We got a guy with character and a guy we are excited to have in the clubhouse."
Lofton received a loud cheer as he ran out to left. The five-time All-Star center fielder could only recall playing there in an All-Star game.
He got tested right away at his new spot when Joe Mauer, Minnesota's No. 3 hitter, hit a fly ball that tailed away from Lofton, who caught it for the third out near the warning track before lofting it into the stands.
"Once I got that out of the way, getting it in a game situation, I was fine after that," Lofton said.
Peralta hit a three-homer in the third off Boof Bonser (5-7) and added a two-run shot in the sixth when the Indians opened a 10-0 lead for Paul Byrd (9-4).
Byrd allowed three earned runs and 10 hits in seven innings, and got the Twins to hit into three double plays.
Bonser gave up six runs and nine hits in 2 2-3 innings.
"A terrible game from our side," Gardenhire said. "We didn't catch the ball or make plays and that's not good enough. It's getting embarrassing and that's what I told them. It's one thing to get beat and one to get embarrassed. That's not how it goes around here and we are not going to start now."
Orioles 4, Yankees 2
Yankees 8, Orioles 7, susp. game
Rookie Jeremy Guthrie limited New York to two runs in six innings and host Baltimore won its fifth straight.
Earlier, the Yankees beat the Orioles in the completion of a game suspended on June 28 by rain. Play resumed in the eighth inning with the Yankees up 8-6, and closer Mariano Rivera gave up a run in a harrowing ninth before earning his 16th save.
That game officially occurred last month, so the Orioles won their seventh straight at home.
