The Twins, sparked by a big game from Justin Morneau, scored 10 times in the second inning and rolled to a 14-3 victory, sending the Indians to their 10th straight loss.
"It was incredible, really, to score 10 runs in an inning," Twins manager Ron Gardenhire said. "It doesn't happen very often."
The Indians, whose last victory came on July 26, have been outscored 88-31 in their losing streak.
"I asked one of my coaches to pinch me tonight because I couldn't believe it was happening again," manager Manny Acta said. "It continues to be rough and disappointing the way we're giving up runs. I don't think I've ever seen anything like it and I don't think I'll see anything like it again."
Morneau homered twice, including the 200th of his career, and drove in four runs, Joe Mauer had three RBIs and Ryan Doumit hit a three-run homer. Ben Revere had four of the Twins' 14 hits and extended his hitting streak to 20 games while Josh Willingham hit his 29th homer, matching his career-high.
The Twins fell one run shy of their biggest inning in franchise history. Minnesota has scored 11 runs in an inning four times.
Scott Diamond (10-5) allowed three runs in seven innings as the Twins beat the Indians for the sixth straight time this season. Minnesota swept a three-game series at Target Field in late July.
Thanks to an assortment of injuries the last two seasons, Morenau, the AL's MVP in 2006, played in 81 games in 2010 and 69 last season. He is the fourth Canadian-born player to hit 200 career home runs, joining Larry Walker, Matt Stairs and Jason Bay.
"It's one of those things I'm able to appreciate," Morneau said. "When you're younger you take it for granted you're going to play until you're 40. You go through some tough times. It's something you can be proud of."
"He's healthy," Gardenhire said. "When you're not healthy and you're trying to go out there and you're playing with something nagging at you all the time, it's tough to play this game."
As a fellow Canadian, Diamond saw special significance in Morneau's milestone.
"I grew up watching him," Diamond said. "He's been a hero to a lot of us."
The Indians went 0-9 on a road trip that ended Sunday. Before Monday's game, general manager Chris Antonetti expressed his support for Acta and the coaching staff even though the team was coming off the least successful trip in the franchise's 112-year history.
The trip ended in shocking fashion when All-Star closer Chris Perez allowed five runs with two outs in the 10th in a 10-8 loss to Detroit. The Indians never had a chance Monday and are two losses from the longest losing streak in franchise history, a 12-game skid in 1931. Cleveland lost 11 straight in 2009.
The Indians loaded the bases with no outs in the first, but scored only one run when Carlos Santana hit into a double play. The brief lead became Cleveland's only highlight when the Twins sent 13 men to the plate in the second.
Zach McAllister (4-4) breezed through the first inning on 12 pitches. The right-hander threw 52 pitches in the second and didn't last the inning. He allowed back-to-back homers to Morneau and Willingham to start the second. Doumit's three-run shot off Josh Tomlin capped the rally. A throwing error by second baseman Jason Kipnis on a ground ball that should have ended the inning made eight of the runs unearned.
The Indians' slump has featured a complete collapse in all phases of the game. Shoddy defense didn't help in the latest loss. McAllister appeared to be out of the inning when Denard Span hit a slow roller to right side with runners on first and third, but Kipnis' throw pulled Santana off the bag at first.
Doumit scored on the play giving the Twins a 3-1 lead. Revere had an RBI single and Mauer, who had three hits, followed with a two-run double. McAllister was finally pulled after a walk to Willlingham and Morneau's RBI single. Doumit greeted Tomlin with his three-run homer.
The Twins hadn't scored 10 runs in an inning since June 4, 2002 against the Indians in Minnesota, a game the Twins won 23-2.
Santana hit a two-run homer in the sixth for the Indians.
NOTES: 2B Tsuyoshi Nishioka, who made two errors, was promoted from Triple-A Rochester before the game. ... Twins RHP Carl Pavano (right rotator cuff) will pitch two innings for Single-A Fort Myers on Tuesday. ... Indians DH Travis Hafner, who homered Sunday, sat out Monday's game with back soreness. ... Antonetti said OF Grady Sizemore (back/knee surgeries) could start a minor league rehab assignment in two weeks. ... Acta said RHP Roberto Hernandez, serving a three-week suspension for age and identity fraud, will make one more rehab start at Triple-A Columbus before rejoining the team. ... Minnesota's Corey Kluber faces Cleveland's Samuel Deduno on Tuesday night.