Kipnis' homer and Santana's sacrifice fly tied the game.
Indians starter Zach McAllister, who hasn't won since April 21, didn't get through the fourth. He allowed four runs and eight hits in 3 1-3 innings.
Chris Young allowed four runs in 5 1-3 innings. The 6-foot-10 right-hander dominated the Indians in his first two career appearances allowing one run in 13 innings. Young allowed one run in five innings in a 3-2 win in Seattle on June 27.
Mariners: Right-hander Danny Farquhar (right upper chest) was struck by a line drive off the bat of Chisenhall in the seventh inning. Farquhar fielded the ball and threw Chisenhall out, but left after talking with manager Lloyd McClendon and a team trainer.
Indians: Left fielder Chris Dickerson (sore left knee) exited in the top of the third inning and is listed as day to day. Dickerson twisted his leg in the second while misplaying Kendrys Morales' double. He was replaced by Mike Aviles.
Seattle left-hander Roenis Elias (8-8) faces Orioles lefty Wei-Yin Chen (11-3) in the opener of a three-game series Friday in Baltimore. Elias' most recent start also came against the Orioles on July 27, taking a no-decision.
Cleveland continues its eight-game homestand Friday when right-hander Danny Salazar (3-4) takes on Rangers right-hander Jerome Williams (2-4). Salazar has won both of his starts since returning to the majors on July 22.
Seattle, which trails Toronto by three games for the AL's second wild-card spot, made two moves to boost the league's lowest-scoring offense. The Mariners acquired outfielder Chris Denorfia from San Diego and then picked up center fielder Austin Jackson from Detroit in a three-team trade that also involved Tampa Bay.
Cleveland traded shortstop Asdrubal Cabrera to Washington. The deal came a day after the Indians traded opening day starter Justin Masterson to St. Louis.