He knew it was a fair ball "when the umpire said it was fair," Santana told reporters after the 6-3 win Tuesday at PNC Park.
The Indians and Pirates were tied at 3-3 before Santana's 10th-inning blast. The Indians first baseman went 2 for 5 with five RBIs and a run scored in the victory.
"We knew the ball was hooking, but it was hit so far over the pole that you couldn't tell," Indians acting manager Sandy Alomar Jr. said of Santana's home run. "It could go either way.
"From what I saw, it looked like it was hugging the foul pole on the fair side and then away on the foul side, but it was too far up there to tell. But it seemed to me like it was a fair ball."
Cleveland began the 10th inning with Cesar Hernandez on second base due to MLB's new rules for the shortened 2020 season. Jose Ramirez struck out in the first at-bat of the half inning. Francisco Lindor was then hit by a pitch, which prompted Santana's stroll into the batter's box.
The Indians first baseman settled in against Pirates relief pitcher Sam Howard. Santana took a ball on the first offering of the exchange. Howard then huffed in a 90.9-mph fastball.
Santana swung and connected with the 1-0 toss and sent the ball 103 feet above the field and watched it sail over the left-field foul pole. The blast traveled 112 mph before it left the field in 5.4 seconds, according to Statcast.
The Pirates asked for a review of the home run to ensure it stayed in fair territory before umpires ruled that the long ball stayed just to the right of the foul pole.
Pirates shortstop Kevin Newman went 3 for 4 with two runs scored and a walk in the loss.
Indians starter Carlos Carrasco allowed five hits and three runs in 4 1/3 innings, but was not on the record for a decision. Pirates starter J.T. Brubaker allowed three hits and three runs in three innings.
The Indians (14-9) face the Pirates (4-15) at 7:05 p.m. EDT Wednesday at PNC Park.