The Tigers failed to take advantage of a two-out baserunning mistake by Jose Ramirez, and Kipnis hit a tiebreaking, three-run homer two pitches later to lift the Indians over the Tigers 4-1.
Ramirez almost broke the tie himself, hitting Shane Greene's 3-1 pitch just past the foul pole down the right-field line, but ended up drawing a walk. Yonder Alonso hit a two-out single into the right-center field gap, and Ramirez stumbled as he took a wide turn around third.
Instead of throwing to third, though, second baseman Dixon Machado sent his relay to the plate, allowing Ramirez to get back to third and Alonso to take second.
''That's a play where, at the worst, we let them have runners on first and third,'' Tigers manager Ron Gardenhire said. ''If Dixon just runs the ball back in, that's what we give them, and if throws to third, we've got a chance at an out. You need to take those opportunities.''
Kipnis then connected off Greene (2-3) for a drive over the right-center field scoreboard for his fourth homer of the season.
''I've only got four this year, but I still know when they are gone,'' he said. ''I caught it flush.''
Kipnis came into the game hitting .205.
''That was a therapeutic trot around the bases, and hopefully this is the start of something big,'' he said. ''I've put a lot of pressure on myself to get this going, but I tried to forget everything right there and just hit my pitch.''
Trevor Bauer (5-4) struck out 12 in eight innings, giving up one run and seven hits. He has fanned 37 in 21 innings over his last three starts.
''I was ready to go back out there for the ninth,'' he said. ''I tend to feel better as the game goes along, and my velocity stays the same or gets better.''
Cody Allen pitched the ninth for his 12th save, staying in the game after being hit by a groundball.
''It got him pretty good, but he's OK,'' Indians manager Terry Francona said. ''He might not pitch tomorrow, but that's because he's been up a lot.''
Tigers ace Michael Fulmer came into the game with a 1-3 record and 6.89 ERA in his past six starts.
Against Cleveland, though, his fastball regularly reached 98 mph as he allowed one run on five hits in seven innings. He struck out seven without walking a batter.
''This was huge, because we've been working on my mechanics, and this is what I needed,'' Fulmer said. ''That's my old fastball and my old command - being able to throw quality fastballs where I need them down in the zone.''
Even after a loss, Gardenhire knew how much Fulmer's performance meant to a team with a banged-up pitching staff.
''That's exactly what we needed to see,'' he said. ''We all knew that he had to get back to commanding the fastball down in the zone, and he did just that.''
The Tigers took only four pitches to grab a first-inning lead on doubles by Leonys Martin and Nicholas Castellanos, but Bauer quickly settled down.
Cleveland tied it in the fourth on Alonso's two-out RBI double. Edwin Encarnacion scored from first, but Alonso was thrown out trying for his third triple in nine major league seasons.
HALL OF FAME COACH
Tigers first base coach Ramon Santiago is away from the team with his wife about to give birth, so Alan Trammell filled in. Trammell, who now works as a special assistant to Tigers general manager Al Avila, will be inducted into the Hall of Fame and have his No. 3 retired later this summer.
Trammell played for the Tigers from 1977-1996 and managed them from 2003-2005.
Bauer threw 113 pitches, increasing his major league-leading average to 109.3 per start. Max Scherzer of the Washington Nationals is second at 106.2. Bauer has thrown at least 100 pitches in all 13 starts this season.
''That's not a big enough lead - I need to bulk that up,'' he said. ''It would definitely be cool if I could lead the majors in that category every year.''
Indians: LHP Andrew Miller (knee) threw a bullpen session before Friday's game. He is likely to throw again during Cleveland's series in Chicago next week.
Tigers: RHP Franklin Perez, generally considered Detroit's No. 1 prospect, is expected to throw off a mound on Tuesday. Perez, acquired from Houston in last year's Justin Verlander trade, has been sidelined since spring training with a lat strain.
The teams play the second game in the weekend series on Saturday, with Cleveland's Mike Clevinger (4-2, 3.36) facing Mike Fiers (5-3, 4.33).
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