Jimmy Howard stopped 13 of the 14 shots he faced in the first two periods before he was replaced by Tom McCollum
Detroit scored four times in the third period against Bruins rookie goalie Malcolm Subban, who finished with 19 saves in Boston's first home game of the preseason.
Justin Abdelkader opened the scoring 5:01 into the game on a power play. The Red Wings scored once more in the opening period and then twice in the second to take a 4-1 lead to the second intermission.
Joakim Andersson, Danny DeKeyser, Daniel Cleary and David McIntyre also scored for Detroit.
Nick Johnson and Jarome Iginla scored for the Bruins.