Howard's homer off Cody Allen (0-3) was his fifth of the season and sixth career game-ending shot.
David Hernandez (1-1) struck out four in two innings of relief for the win. Five Phillies pitchers combined for 18 strikeouts.
Philadelphia's bullpen pitched six scoreless innings and struck out 11.
The Phillies have won seven of eight and have looked little this season like a team picked to finish last in the NL East.
Jason Kipnis hit a two-run homer for the Indians, who struck out 14 times against four Phillies pitchers through nine innings. Hernandez struck out the side in the 10th to keep the Ks going.
Maybe it seemed fitting that on the night Pearl Jam cranked out top tunes from its heyday across the street at the Wells Fargo Center, the Phillies turned back the clock and revisited their own greatest hits in the fifth:
Howard and Carlos Ruiz gave Phillies fans an October flashback with consecutive doubles that made it 3-2. Howard, the much maligned and longest-tenured Phillie, singled and doubled in his first two at-bats to boost his .185 average.
Howard and Ruiz are the only Phillies left from the 2008 World Series championship team that once made a ticket at Citizens Bank Park the toughest in town. The holdovers played Friday in front of just a few thousand fans on a chilly night that whipped around those glory days pennants in left-center much in the same manner fans would twirl rally towels during another postseason run.
The Phillies tied the game 3-all in the fifth and had chance to go ahead in the sixth with a runner on second and two outs.
But reality seemed to hit that it's 2016 and not `08 - Howard whiffed in the clutch against Indians starter Corey Kluber to end the threat. He also grounded out with a runner on in the ninth.
Howard, though, can still turn on that power stroke.
The fifth-inning rally took starter Adam Morgan off the hook. He allowed five hits, walked one and struck out a career-high seven in five innings.
He gave up all three runs in the fifth when Kipnis hit a two-run shot to right for his third of the season. The lefty-swinging Kipnis went deep against Morgan, the first lefty starter this season for the Phillies.