Dylan Larkin also had two goals for Detroit, and Filip Hronek also scored. Jimmy Howard made 35 saves as Detroit won for the sixth time in seven games.
In the third period, the Red Wings took a two-goal lead for the second time — only to see the Sabres come back for a second time.
Larkin made it 3-2 on a highlight-reel effort 6:44 into the third. The Red Wings' leading scorer picked the puck up behind the right circle and spun all the way to the left circle, beating Ullmark with a wrist shot through traffic.
Larkin's second came with 6:56 remaining. With Ullmark out of position following a Sabres defensive breakdown, Larkin finished a one-timer for his 30th goal of the season. Larkin became the first Detroit player since 2008-09 to score 30 goals in a season.
The Sabres stormed back with a pair of goals in a span of 41 seconds.
Showing patience in front of the net, Mittelstadt scored his 12th goal of the season from close range with 4:59 remaining.
Eichel evened the score at 4 moments later, finishing a breakaway after a setup pass by Victor Olofsson, who was playing in his first NHL game.
Bertuzzi opened the scoring on the power play with 7:58 remaining in the first period.
Hronek made it 2-0 just one minute into the second on an odd-man rush with Sabres winger Sam Reinhart coming back late.
The Sabres then responded with two goals of their own. Okposo cut Detroit's lead to one with a power-play goal 6:12 into the second, scoring on a wrist shot for his first goal in nine games. Scandella evened the score with 2:44 left in the period, collecting a pass from Zemgus Girgensons.
Detroit center Frans Nielsen left the game with an apparent head injury with 8:17 remaining. Nielsen collided with teammate Luke Witkowski and Buffalo's Kyle Okposo before going down to the ice.
NOTES: The Sabres were without two of their top defenseman in Rasmus Ristolainen (illness) and Zach Bogosian (lower body). Ristolainen missed his second straight game, Bogosian missed his third game in a row. ... D Matt Tennyson, D Jake McCabe, LW Scott Wilson, D Matt Hunwick and LW Evan Rodrigues were also scratched for Buffalo. ... Before the game, the Sabres demoted C Tage Thompson to the minors. Thompson, a former first-round pick of the St. Louis Blues, is in the midst of a 23-game goal drought. ... D Mike Green, LW Justin Abdelkader, LW Thomas Vanek, C Michael Rasmussen, RW Martin Frk, C Jacob de la Rose and D Trevor Daley were scratched for Detroit.
UP NEXT:
Red Wings: Home against New Jersey on Friday.
Sabres: On the road against the New York Islanders on Saturday.