Micheal Ferland and Johnny Gaudreau scored for the Flames.
Andreas Athanasiou and Anthony Mantha each scored a pair, while Gustav Nyquist, Dylan Larkin, Justin Abdelkader and Luke Glendening did the damage for Detroit.
Eddie Lack had his second start as a Flame, but left the game after giving up five goals on 15 shots over 24:27 of play. Jon Gillies, up from the Stockton Heat on an emergency recall while Mike Smith remains sidelined with an injury, subbed in for him, surrendering three goals on 12 shots the rest of the way.
"I don't think we were prepared to play," coach Glen Gulutzan said following the game. "We were light on our sticks and that was evident in the goals. I thought that we didn't get any big saves early, but I don't know which one (Lack) was supposed to get."
For the Red Wings, Jimmy Howard stopped 26 of 28 shots.
Just over five minutes into the game, Athanasiou got the Wings on the board, capitalizing off of an early turnover. With Detroit bearing down three-on-one, TJ Brodie dropped down to try to take Athanasiou's pass away, but by swinging his stick, he knocked the puck into his own net instead.
"Felt like I was fighting it all night," Brodie said. "It's definitely not the way I wanted to play tonight, and you know, the more you dwell on it, the more it affects you, the more negative it becomes, so I think just moving on from it is the best."
Less than two minutes later, Nyquist scored off of a Red Wings rush into the Flames' zone. Thanks to Mantha lifting Travis Hamonic's stick, Nyquist found himself one-on-one against Lack and beat him in the slot, sniping the puck glove-side.
Soon after, Nyquist was sent off for high-sticking Brett Kulak, giving the Flames the first powerplay of the game. They scored, thanks to Ferland's fantastic effort against Howard. While Howard stopped Gaudreau's initial shot, Ferland continued to whack away at the puck until it trickled underneath Howard's pad and just across the goal-line, bringing the Flames back within one.
The Red Wings, however, responded with a powerplay goal of their own. With Mikael Backlund off for interference, Mantha beat Lack to his own rebound, scoring in tight to restore the Wings' two-goal lead.
The Flames had another powerplay opportunity to close out the period, with Luke Witkowski sitting in the box for cross-checking Ferland. However, Kris Versteeg fell inside the blueline, giving Detroit a shorthanded two-on-one. Larkin outlasted Brodie, waiting for him to drop down, before sniping it in the top corner, far side, beating Lack.
"It certainly wasn't the first period that we had drawn up, and we just couldn't get back into it," Hamonic said. "We were chasing the game right from the start.
"We gotta clean it up. Have a good push in the next couple of games on the road here, for sure."
Lack's night ended early in the second period. With Backlund in the box again - this time for tripping Henrik Zetterberg - Mantha scored his second of the night, tipping Frans Nielsen's shot up and over Lack.
Gaudreau was able to breathe some life back into the Flames, as he and Dougie Hamilton initiated a rush up the ice. Hamilton dished the puck off to Ferland inside the offensive zone, and Ferland sent a cross-ice pass Gaudreau's way. Gaudreau made no mistake on the shot, snapping it high blocker side to beat Howard.
However, with just under a minute to go in the second period, Abdelkader capitalized off of a Larkin dump-in. The puck bounced off of the boards and right to Abdelkader, who whacked it past Gillies, short-side, to restore Detroit's four-goal lead.
"I think we had chances," Brodie said. "I think it was one of those games where we'd score and we might get a chance after we score to decrease their lead, and we don't score on that, and then they come down and the next chance they get they score, and they're back up by the same lead they were just up by. So it's one of those games, and it's definitely frustrating."
In the third period, Kulak had his first career fight with Witkowski. The Flames took exception to Witkowski's continuing the fight when Kulak was down, resulting in a line brawl, and a five-minute powerplay for Detroit - including a two-minute five-on-three - to close out the game.
"You got one of their heavyweights, tough guy, going after Kuly, and as a group we want to try and stick up for each other," Hamonic said. "Next thing you know, you get into a fight, and you think everything's fine, and (it) turned into UFC match on their bench."
Athanasiou scored his second of the night on the five-on-three, roofing the puck over Gillies. Glendening had the final goal of the game, thanks to a bounce off of Gillies around the crease.
Gaudreau has an eight-game point streak, tying his career high. He has 14 points over that time. He has had three other eight-game point streaks in his career, with 12 points over each of them … Ferland has scored in five straight games, and has six goals in his last seven … This was Gillies' second NHL appearance, and first in relief.
The Flames won't play again until Saturday, when they'll take on the Philadelphia Flyers in an 11 a.m. MT matinee. They'll continue their six-game road trip from there, with their next stops being in Washington (Monday, 5 p.m. MT), and Columbus (Wednesday, 5 p.m. MT).