With Cleveland trailing 3-2 and Yan Gomes, who had walked, on first, Lindor pounded a 2-0 pitch from Chris Devenski (1-1) over the wall in center field. Lindor's sixth home run was estimated at 456 feet.
Indians starter Corey Kluber (3-1) struck out 10 in seven innings. He allowed three runs on eight hits and four walks. Bryan Shaw retired the side in order in the eighth, and Cody Allen pitched around three hits in the ninth to earn his fifth save.
Houston took an early lead in the top of the second inning when Marwin Gonzalez hit an 0-2 pitch from Kluber over the center field wall for a solo shot. The homer improved Gonzalez's career average vs. Kluber to .462 (6-for-13) with two home runs and six RBIs.
The Astros' 1-0 lead didn't last long. Edwin Encarnacion led off the bottom of the first inning by hitting Mike Fiers' first pitch over the left field wall for his fourth home run.
In the third inning, the Astros sent eight men to the plate, and two of them scored. With one out, Carlos Correa doubled and went to third on a single by Brian McCann. Evan Gattis followed with a single to left field, scoring Correa to give Houston a 2-1 lead.
McCann went to second on the hit by Gattis. Kluber retired Yulieski Gurriel on a popout for the second out, but Alex Bregman's bloop double down the right field line scored McCann to make it 3-1.
The Indians got a run back in the fifth inning when for the second time in the game, Fiers gave up a home run on his first pitch of the inning. This time it was by Abraham Almonte, who hit one over the wall in center to cut the Astros' lead to 3-2.
Gomes followed Almonte's homer with a double down the left field line.
NOTES: Astros 2B Jose Altuve did not start the game, but he singled as a ninth-inning pinch hitter. Altuve continues to recover from a jarring collision with OF Teoscar Hernandez on Tuesday. Marwin Gonzalez replaced Altuve at second base. ... Houston's 7-6 loss to Cleveland on Wednesday marked the first time the Astros scored four or more runs in a game and lost. They are 10-1 in those games. ... RHP Carlos Carrasco will start for the Indians on Friday night at home against the Seattle Mariners and LHP Ariel Miranda. ... The Astros will throw RHP Charlie Morton against the Oakland A's and RHP Jharel Cotton at Houston on Friday. ... Indians RHP Cody Allen's four-out save in Wednesday's game was his 17th in which he recorded four or more outs. His ERA in those games is 0.77.