Raymond and Dylan Larkin each had a goal and an assist, and Thomas Greiss made 33 saves for Detroit (8-7-2), which had won four of five.
"We were poised, we made plays, but just when we got the lead we didn't keep our foot on the gas and keep playing and keep making it hard on them," Larkin said. "Teams are too good, the League is too tight every night to play half the game. We've got to play a full 60 minutes."
Larkin gave Detroit a 1-0 lead at 14:45 of the first period with his seventh goal of the season.
Michael Rasmussen scored his first goal in 28 games at 4:23 of the second period to make it 2-0. He was along the left wall when Vladislav Namestnikov dropped a pass for a quick shot from 42 feet.
"I thought our first [period] was good and then after that I didn't think we played good enough hockey," Red Wings coach Jeff Blashill said. "I thought we're fortunate to have the lead, to be honest, and we made a couple of mistakes, and the next thing you know it slips away from you.
"We've talked about learning lessons while we're winning. But sometimes you've got to get slapped in the face, and we got slapped in the face tonight."
Boone Jenner cut it to 2-1 at 13:07 with a rebound of Nyquist's shot. Jenner leads Columbus with seven goals.