But there's a good chance that Cleveland manager Terry Francona will be putting his designated hitter back in the leadoff spot on occasion.
With Jose Ramirez and Rajai Davis not playing Friday night, Francona decided that Santana and his .364 career on-base percentage -- and the fact he has walked more than 100 times the last two years -- would be a good match for Detroit right-hander Justin Verlander.
Santana clubbed a leadoff home run on a 3-2 pitch to get Cleveland started and the Indians got a tiebreaking home run from Marlon Byrd on Verlander's first pitch of the seventh inning in a 2-1 victory over the Tigers.
Josh Tomlin (2-0) and three relievers combined on a four-hitter. Verlander (1-2) gave up four hits in seven innings and struck out 10 for the 30th time in his career.
"I thought he (Santana) did a good job," Francona said. "A home run his first time up and a double his second. That's as good as you can draw it up.
"Who knows? He might have hit a two-run home run batting cleanup."
Santana has seven career home runs in his matchups against Verlander.
"Tito put me in the lineup," Santana said. "I don't worry about where, just about my team winning. I don't know (why I hit Verlander so well)."
Batting leadoff is something that Francona had talked over with Santana on occasion during spring training and earlier this season.
"I'd rather have a slow guy who gets on base leading off than a fast guy who doesn't," Francona said. "If a fast guy can't get on base, all he's only fast getting back to the dugout."
"It's kind of a mixed bag," Detroit manager Brad Ausmus said of the Santana-Verlander matchups. "He doesn't necessarily hit him all the time, but when he does hit him it's damage.
"For some reason since I've been here, it seems when he connects with the ball the ball seems to travel a little bit. With that being said, Santana aside, Verlander was nearly flawless. But unfortunately Santana was (in the lineup)."
Santana's home run was his third of the season and Byrd's was his second. Both were shots to right center off Verlander.
"You know, you always feel like you left something out there when you lose a game 2-1 or 1-0," Ausmus said. "Verlander was outstanding. He really was. That's one of the better games he's thrown in the last year and a half. He did his part. Unfortunately, Tomlin did a little bit better."
Tomlin lasted 6 2/3 innings, also giving up four hits with a walk and four strikeouts.
"Josh pitched really well," Francona said. "It was fun to watch. That was one of the better-pitched games we've seen this season."
Zach McAllister came on to strike out pinch-hitter Jarrod Saltalamacchia with a runner in scoring position to end the seventh. Brian Shaw worked a clean eighth and Cody Allen the ninth for his fifth save.
Miguel Cabrera went 0-for-3 and saw his batting average dip to .220. The players hittiing around him aren't on fire either. Justin Upton is down to .227 with 27 strikeouts in 66 at-bats and Victor Martinez is at .261.
"There was nothing in particular that was a problem with the bats," Ausmus said. "We just didn't score runs. We hit a few balls hard, but we didn't do anything with Tomlin. He was too good."
NOTES: Indians DH Carlos Santana led off for the first time in his major league career. "I think this is the first game Jose (Ramirez) or Rajai (Davis) haven't played," manager Terry Francona said. "He won't be leading off Saturday." His career on-base percentage is .364. ... Slumping CF Anthony Gose was absent from the Tigers' starting lineup for a second straight game. "I don't think it hurts sometimes to have more than one day off," manager Brad Ausmus said. ... Cleveland LF Michael Brantley will play back-to-back minor-league games this weekend as a possible end to his rehab assignment. "From my side of it," Francona said, "the good news is he feels really good." He could rejoin the Indians early next week. ... Injured Detroit C James McCann (right ankle) could begin a brief rehab assignment in a few days.