The righty struck out nine Angels courtesy of a high-90s fastball that registered a career-high 101 mph -- in the eighth inning -- but the streaking Angels rallied with Scherzer out of the game to pull out the win.
Octavio Dotel came in to relieve Scherzer and he allowed three singles, including Callaspo's that scored pinch-runner Peter Bourjos. Prince Fielder hit his 25th homer and Alex Avila hit his eighth.
The Tigers fell even further back in the Wild Card race, now 3 1/2 games behind the second Wild Card team, the Orioles, and now sit 1 1/2 games behind the Angels, who have won nine of their last 10. Detroit remains one game back of Chicago in the AL Central division with a four-game series coming up next week.
"We're in the AL. You could look around the whole league and make a case for everybody," Scherzer said. "The Angels are no different. Don't get me wrong, that's a great ballclub over there with what they can do with so many facets of the game -- pitching, baserunning and obviously the middle of the lineup. Obviously, they are going to be a contender all the way until the end.
"We know how much time we have in this clubhouse," he added.
On Friday, the offense didn't back up the righty's great performance. Scherzer came into the game with five wins in his last five starts while allowing just four earned runs in 35 innings with 44 strikeouts, with one of those wins against the Angels last month in Detroit.
He even hit triple digits on the radar gun for the first time in his career and the fact that it came in the eighth inning when he was well over 100 pitches made it even more impressive. But manager Jim Leyland didn't even consider bringing the hurler back out in the ninth despite the fact that his velocity wasn't decreasing one bit, even after 110 pitches.
"There was no way I would send him back out there in the ninth," Leyland said. "That was a no-brainer."
But with Scherzer out of the game and Dotel in, things began to unravel for the Tigers thanks to some bad luck and good bounces for the Angels. With one out, Kendrys Morales laced a single to center off Dotel (5-3) and Erick Aybar hit a nubber to third with Miguel Cabrera playing back for an infield single, moving pinch-runner Peter Bourjos to second. The next batter, Callaspo, singled into left.
The most frustrating part for Leyland was actually the top half of that inning, when Delmon Young led off with a single and pinch-runner Quintin Berry stole second. Ernesto Frieri (4-0) got the next three batters out to escape the jam.
"We caught a break on the steal, didn't take advantage of it," Leyland said. "They got a little nubber in the infield in the last inning to keep the inning going and they did take advantage of it. Simple as it is."
Scherzer was shaky out of the gates and let the Angels jump out to an early lead with three hits and two runs in the first. Mike Trout, whom the Tigers held to just an infield single in three games two weeks ago, led off with a double to center.
He scored on a single by Torii Hunter up the middle one batter later and the Angels picked up another run in the inning on a Howie Kendrick groundout that scored Albert Pujols.
However, Scherzer settled down and the Tigers answered right back with a pair of homers in the second and third coming off the bats of Fielder and Avila to tie the game.
"That guy is nasty," said Ervin Santana, who started in place of Jered Weaver and struck out 10 in 6 2/3 innings. "He is very nasty and we were able to get a few runs against him, which was great. He has tremendous stuff and had great location tonight."