The 383-foot blast helped the Indians hold off a furious comeback attempt from the Twins at Cleveland's Progressive Field. Cleveland held a 3-0 lead entering the top of the seventh inning, but Minnesota responded by plating three runs in the inning to tie the score.
Twins reliever Trevor May retired the first two hitters he faced in the bottom of the frame, before Santana stepped into the box. The Indians slugger fouled off the first two pitches he received from May. The Twins right-handed pitcher then heaved in an 80.8 mph curveball.
Santana swatted the pitch over the right field fence for his 21st homer of the season, giving Cleveland the go-ahead run.
Santana was 1-for-2 with two runs scored, an RBI and two walks in the win. He is now hitting .294 on the season with with 54 RBIs, in addition to his 21 long balls.
Indians third baseman Jose Ramirez was 1-for-4 with an RBI in the victory. Indians outfielder Tyler Naquin was 2-for-3 with an RBI. Left fielder Greg Allen plated Cleveland's other run with an RBI single in the fourth inning.
Marwin Gonzalez was 3-for-4 for the Twins.