Casey Kotchman went 3-for-4 and knocked in the go-ahead run in the sixth inning, as the Indians upended the Tigers, 5-3, in an AL Central battle.
Travis Hafner knocked in a pair for first-place Cleveland, which had dropped its final 10 meetings against its division rival last season.
Ubaldo Jimenez (5-3) labored through six innings but still wound up with the victory as he allowed three runs on five hits and six walks. Chris Perez retired Miguel Cabrera and Prince Fielder with runners on the corners in the ninth to preserve to club's sixth win in eight games.
"We had a lot of good at-bats up-and-down the lineup...and our bullpen was very good again," Indians manager Manny Acta said.
Alex Avila provided Detroit's offense with a three-run homer in the second inning, while Rick Porcello (3-4) was tagged for five runs -- four earned -- on eight hits over 5 1/3 innings in defeat.
The Tigers were trying to open a 10-game road trip with consecutive wins for the first time since mid-April.
Hafner knocked in Shin-Soo Choo in the third and fifth innings, first on a single, then on a sacrifice fly to tie things at 3-3.
Cleveland played small-ball in the sixth to push two more across. Michael Brantley led off with a single, stole second and scored on Kotchman's one-out base hit to center. Kotchman advanced 90 feet on Porcello's throwing error and came around when Brennan Boesch couldn't come up with Jose Lopez's sinking liner to right.
Tony Sipp and Joe Smith combined to throw a scoreless seventh, and Vinnie Pestano set down the side in order in the eighth.
Perez allowed a one-out walk and an Andy Dirks single prior to retiring the heart of Detroit's lineup, as he caught Cabrera looking at strike three and got Fielder on a weak grounder to the left side to lock up his 14th save.
"We didn't muster enough runs. We had enough opportunities," Tigers manager Jim Leyland said.
Asdrubal Cabrera doubled high off the wall in left-center to knock in Jason Kipnis in the Indians' first at-bat, but the Tigers went in front on Avila's home run.
Boesch reached on a double to right and Jhonny Peralta worked a walk prior to the blast, which landed in the bullpen beyond the wall in right-center.
Both teams left 10 runners on base...Jimenez had a 6.35 ERA in five starts against the Tigers last season...Porcello fell to 5-2 lifetime against Cleveland...Before the game, the Tigers placed second baseman Ryan Raburn on the bereavement list and recalled infielder Danny Worth from Triple-A Toledo.