Simon Edvinsson and Daniel Sprong scored, and J.T. Compher had two assists for Detroit.
Xavier Ouellet scored for Pittsburgh. Alex Nedeljkovic made 22 saves.
Ouellet gave the Penguins a 1-0 lead at 17:38 of the first period, scoring with a backhand off an assist from Jansen Harkins.
Sprong scored his third of the preseason on a slap shot near the blue line to tie it 1-1 at 5:32 of the second period.
Edvinsson, who was the No. 6 pick in the 2021 NHL Draft, put the Red Wings ahead 2-1 at 13:14 of the third period. He scored with a wrist shot from the left circle during a 4-on-4.
