Jimmy Howard made 35 saves to cool off the Coyotes, who have dropped their last two home games after winning 10 straight in Glendale.
Ilya Bryzgalov stopped 32-of-35 shots and Matthew Lombardi scored on a power play at 5:35 of the second period.
Lombardi's goal tied the game 1-1 after Holmstrom redirected a shot by Niklas Lindstrom late in the first period to put Detroit ahead 1-0. Lindstrom and Holmstrom teamed up for another redirected shot that put the Wings back on top 2-1.
Datsyuk made it 3-1 at 5:51 of the third period and Helm knocked in an empty-netter with 51.1 seconds left in regulation to close out the scoring.