The Tigers' shortstop committed his second error of the inning on the next play, as Peralta's throw to first base on a grounder by Starlin Castro forced Prince Fielder to lean to his right. It appeared Fielder's foot may have still been on the bag on a bang-bang play, but Castro was ruled safe at first as the Cubs scored the go-ahead run.
Reliever Phil Coke (1-3) took the loss, pitching two innings and allowing just the one unearned run.
"I was pretty confident that Santiago not only beat the runner to the bag, but the throw beat the runner to the bag at second base, and I guess we could go look at the replay and see what it says," Coke said. "I knew for a fact [Castro] was out at first base, because there's no way that [Fielder's] body came off the bag with the ball not in his glove.
"There's no way. He's pushing off of the bag to get to the ball. ... I'm not saying anything ill toward anybody, I want to be very clear about that. It is what it is."
After scoring four runs in the eighth inning on Sunday to win by one run, the Tigers scored three runs on two run-scoring hits off reliever Casey Coleman to tie the game at 3 in the seventh inning on Tuesday.
The inning began on a double by Delmon Young on another close play at second base, where it appeared Darwin Barney may have made the tag.
"I had my back turned and I kind of went right in front of [the umpire's] line of sight and threw myself in front of the bag," Barney said. "It looked like I got him."
A walk by Peralta chased Cubs starter Paul Maholm, who struck out a season-high seven, and brought in Coleman, who allowed an RBI single to pinch-hitter Santiago and a two-run single to Austin Jackson.
"We gave ourselves a chance," said Tigers manager Jim Leyland. "It's a tough way to lose when they don't hit a ball out of the infield and you lose the game. That's all part of it. [Campana's] got real good speed; he can create some problems for you."
The Tigers managed to get hits off Maholm throughout the game, with singles in the second, third, fourth and sixth innings, but failed to string any together until he left in the seventh.
Fielder and third baseman Miguel Cabrera both hit deep flies against Maholm that were pushed back into the park with the wind blowing in.
"That's Wrigley Field," Leyland said. "Some days it blows out, some days it blows in. Thursday afternoon it could be blowing out. That's part of the game."
Tigers starter Max Scherzer kept the game within striking distance, allowing three runs and fanning eight in six innings. He said it was difficult to helplessly watch the eighth inning unfold.
"The umpires have a tough job," Scherzer said. "We're asking them to be perfect. I wish there was a way we could have review, I wish there was a way something like that could be corrected. That's an extremely tough call."
Scherzer struggled with his command at times, walking five, including one intentionally. The three Cubs who scored in the first six innings all reached base via walks. Scherzer had allowed more than three walks only one other time this season.
"For the most part, I was working both sides of the plate," Scherzer said. "I walked too many batters there, besides the intentional walk. My job is to not give those free passes out. Other than that, I thought I was attacking the zone."
The loss snapped Detroit's seven-game winning streak against the Cubs and dropped the Tigers to 4-3 in Interleague Play this season.