Santana, Cleveland's first basemen, got plunked in the back by Detroit Tigers starter Jordan Zimmermann in the fifth inning. Santana yelled at Zimmermann before taking first base, but no one was ejected.
The following inning, the Indians erupted in a constructive way.
Jose Ramirez's two-run homer capped a four-run sixth inning and the Indians salvaged the second game of a day-night doubleheader with a 4-1 victory over the Detroit Tigers on Saturday night at Comerica Park.
Three Detroit batters had been hit by pitches during the day before the pitch that whizzed behind Santana.
"A couple of their guys got hit. I understand that. But I don't think you ever throw behind somebody," Cleveland manager Terry Francona said. "Looking back, though, it might have been the best thing that happened to us because it woke us up and our guys really got after it from there. We played with a lot more energy."
Carlos Carrasco (9-3) held the Tigers (36-44) to one run and four hits in seven innings. Carrasco bounced back from an outing in which he gave up eight earned runs in 3 1/3 innings against Texas on Monday. Andrew Miller posted his second save.
Carrasco retired the last 10 batters he faced after hitting Tigers shortstop Jose Iglesias with a fourth-inning pitch.
"I don't want to hit anyone. I just want to get a ground ball to get an out," Carrasco said. "The game's 1-0 and a man on (second), I don't want to hit anyone. I was just trying to throw inside to get a ground ball and that hit him. After that, I started to pitch a little more aggressive."
Zimmermann (5-6) gave up four runs and five hits in 5 2/3 innings. He held Cleveland to one hit before the sixth.
"That's the way it's been going for me," Zimmermann said. "I've been pitching well and I'm just not getting the results."
Zimmermann said there was no intent on the pitch to Santana.
"I got him out the first time up and in," he said. "I was having a tough time all night going in on lefties. Everything kept running back, running back. I told myself 'Drive it in there.' I drove it in there and threw behind him.
"I don't know what he was saying. I couldn't understand him. Obviously, he was upset and probably thought it was intentional, but it wasn't."
Mikie Mahtook had two hits and drove in Detroit's run.
The Tigers won the opener 7-4, breaking a 4-4 tie with three runs in the seventh inning. Nicholas Castellanos had three hits, including a go-ahead triple in the seventh, and J.D. Martinez and Miguel Cabrera hit back-to-back homers for Detroit.
Brantley's RBI groundout brought in the first run and Encarnacion's bloop single knocked in the second run. Ramirez then crushed the next offering into the right field stands, making it 4-1 and ending Zimmermann's night.
The Tigers grabbed the early lead in the second inning. Castellanos led off with a double and one out later Mahtook brought him home. Mahtook checked his swing and he made enough contact to bloop the ball over second baseman Jason Kipnis for a single.
NOTES: Detroit LF Justin Upton missed both games of the doubleheader because of right side soreness. Upton was a late scratch in the opener after feeling discomfort in the batting cage. Upton leads the club in homers (15) and RBIs (52). ... The Tigers haven't swept a doubleheader from the Indians since Aug. 7, 1986. ... Cleveland is 36-10 when scoring four or more runs. ... Indians 3B Jose Ramirez stretched his road hitting streak to 14 games with his sixth-inning home run. ... Detroit ace RHP Justin Verlander (5-4, 4.47 ERA) opposes RHP Mike Clevinger (3-3, 3.56) in Sunday afternoon's series finale.