It snapped a five-game winning streak for the road team in this series.
Darren Helm (two) scored for the Wings, who fell to 14-40-4. Helm, Anthony Mantha and Frans Nielsen all returned to the lineup after missing time with injuries.
Conor Sheary, Marcus Johansson and Sam Reinhart scored for the Sabres, who now move above the .500 mark at 25-24-8.
Detroit goaltender Jonathan Bernier (12-15-2) made 22 saves.
Buffalo netminder Carter Hutton (9-9-4) had 27 stops.
Up next for the Wings is a day off before playing the Devils in New Jersey Thursday night.
The Sabres welcome the Columbus Blue Jackets to town Thursday night.
1. Darren Helm: Helm was not out long, just two games with an undisclosed injury, so it was not surprising to see him come out of the gate fast. Starting on the top line with Dylan Larkin and Mantha, Helm got the first three shots on Hutton and got his own rebound into the net just 27 seconds into the first period. Mantha, who missed considerably more time -- 20 games with broken ribs and a punctured lung -- got the lone assist. It was Helm's first goal since Dec. 28 at Florida, snapping a 16-game goalless streak. At 7:02 of the second period, it was Helm again, this time alone in front of the net backhanding the puck past Hutton for a 2-1 Detroit lead. Mantha again assisted. Last season Helm had seven goals in 61 games. Now he has eight in 55 games this season. Helm finished with 24 shifts for 16:23, had a team-high five shots and was plus-1.
Quotable: "I try to keep things as simple as possible. Our line had some energy and I was able to find a way way to get some decent forechecks and a couple of goals. Compared to all the other ones (seasons), it's gotta be the worst one I've been a part of. That's hard for everybody. Old guy, young guy, it's not easy to be in this situation. It's a good thing that I think we're still working pretty hard. We're still coming out with some energy. It doesn't always go great for us but we're still competing." - Helm
Quotable II: "He missed a couple of games, too. Two, three games, right? And came back with two goals, so he played a great game. Great bumper on the first goal and then great bumper on the second goal." - Mantha
Quotable III: "Helm's had a good year when you look at it. I think he scored his seventh and eighth goals tonight. I think he'll move to minus-2, which on our team, when you get to comparisons, it's a pretty good number. He works, he competes every night, he competes every shift, he's been more physical probably this year than the last couple of years. He creates offense out of his speed and compete and he's good defensively because of that. So he's had a good year." - Wings coach Jeff Blashill
2. Anthony Mantha: Of the last 32 games coming into Tuesday, Mantha had played in just four. The latest injury occurred Jan. 21 in Toronto when Maple Leafs defenseman Jake Muzzin slew-footed Mantha. The unpenalized and unpunished action broke Mantha's ribs and punctured his lung. For the first three weeks, Mantha couldn't do a thing while the lung and ribs healed. But Mantha's timing did not seem to be missing as he found Helm for both of his goals, one early in the first and the other midway through the second. Mantha now has 26 points (12-14-26) in 30 games. Mantha finished with 27 shifts for 19:36, had four shots, two hits and was plus-2.
Quotable: "It looked like it. The legs were a little heavy today but that's something I was expecting. Obviously it feels good to get right in the mix. I think I played a lot of minutes tonight, so hopefully it comes back quick. Play great hockey for 20-something games, whatever is left for me. Obviously maybe a goal would be a point a game until the end of the season. That's personal but like I said this morning, getting a couple of wins together for next year and things like that would be great." - Mantha
Quotable II: "He played a great game. He's a big body for us, he moves his feet really well. I think for a guy that's missed that much time, I don't think I've ever seen someone come back and look like they haven't missed a beat, so you could tell the past seven weeks he's been out, he's done everything to give him a chance and be ready for his first game back. For a guy that's gone through a lot this year -- there was talk he might not even be able to play this year -- he got cleared and came back and was our best player out there tonight. We're going to need him moving forward and it's a great sign he was back playing that way." - Dylan Larkin
Quotable III: "He came out with lots of energy and was handling the puck and showed poise with it. I think at times, he calmed things down a lot. Obviously he's a great player. This team needs him to be healthy to be successful. I'm excited to see what he can do the last few games that we've got." - Helm
Quotable IV: "I thought Anthony played really good. When he came back last time, he never really got going at the level that he's capable of. I thought this time right off the bat, he was skating well, in on the forecheck, physical, good hands, ripping shots. I thought the line was really good. I thought Darren Helm played really well. Larks played well. It was good to have Anthony back playing at that level. When he plays at that level, he's one of the better players in the league. He's really hard to handle. He's got a really unique skillset of size, speed, hands, shooting, passing. If he can keep playing at that level, it makes us a way better hockey team." - Blashill
3. Brendan Perlini : It was a very scary sight at 16:09 of the first period as Perlini and Buffalo defenseman Henri Jokiharju were battling along the boards and Jokiharju's skate came up and cut Perlini's face as both fell. The referee blew the whistle immediately as head athletic therapist Piet Van Zant and assistant athletic therapist Russ Baumann rushed to attend to Perlini. They helped Perlini off the ice, holding a towel to his face. The team announced in the second period that team doctors in Buffalo were stitching up Perlini's nose, which suffered a deep laceration. At the time, Perlini's return was questionable but he did not end up playing the rest of the game. Perlini played four shifts for 3:49, had one shot, one blocked shot and was even.
Quotable: "It was really scary. He's a great player, he's just starting to hit his stride with us. To see that, from the bench we got a pretty good look, it's scary sight anytime a guy gets a skate like that up high. Seemed like it was kind of slow motion, too. It came across and got him. It obviously wasn't intentional. It was just a scary play. He's doing all right. I just spoke with him back there, he's feeling better. He's a tough guy, we're happy he's all right." - Larkin
Quotable II: "Anytime you see skates coming up, it's scary. I haven't seen the aftermath of it. I hope he's doing fine. I heard it's pretty bad but he's a tough guy and hopefully he'll be back soon. That's a risk we're all taking. I think everybody's had a close call, or had something similar to that happen. You just gotta find a way to shrug it off and keep going." - Helm
Quotable III: "I just talked to Brendan and talked to Piet Van Zant as well. Brendan is doing good. He's up. It cut him underneath the eye and around the nose. Basically, he has a large facial laceration in the nose area. I think he was thankful, I was thankful, we were all scared when it first happened, when we first saw it, that it had gone near his eye. That's the thing you're most worried about. It's just an unfortunate situation where the skate came up and he was falling and it caught him in the face. Super scary. At that point, I think both teams just worried about his well-being. Thankfully, he's going to be all right." - Blashill
Quotable IV: "It looked terrible. We kind of saw it coming in slow motion on the ice. Hopefully he's fine. I didn't see him between periods. He showered and went somewhere. Hopefully he's fine. Either team, you don't want to see a skate to the face, no matter how much hate you have against a guy. It's just a terrible thing. Hopefully he's fine, like I said. The only good thing was he got up. Piet said he should be fine. Hopefully he is." - Mantha