Brad Stuart, Tomas Holmstrom and Patrick Eaves also scored for Detroit. Ruslan Salei and Nicklas Lidstrom each had two assists, and Chris Osgood made 23 saves.
Joel Ward, Kevin Klein had goals for Nashville, which has dropped two straight in regulation after earning at least one point in each of the first eight games this season. Pekka Rinne stopped 23 shots.
Datsyuk gave Detroit a 1-0 with 7:49 left in the opening period when his shot from the right circle caught Rinne down and out of position. Stuart's first of the season made it 2-0 with 1:36 remaining in the frame. The usually defensive-minded defenseman made a rare trip deep into the offensive zone and poked in a loose puck from just outside the crease.
Ward cut the Predators' deficit to 2-1 at 7:49 of the second, beating Osgood between the pads from the slot for his second goal.
Datsyuk's second of the night and sixth of the season restored Detroit's two-goal edge with 1:18 left in the second period. He powered his way out of the right corner, beating forward Nick Spaling, went to the net and stuffed the puck past Rinne.
Holmstrom's power-play goal 4:18 into the third made it 4-1. Holmstrom tipped in Lidstrom's shot from right point for his third goal. Eaves added his second 2:08 later, and Klein finished the scoring with 9:39 left.
Notes: Detroit G Jimmy Howard missed his second game because of back spasms. ... Red Wings F Justin Abdelkader made his season debut after missing the first eight games because of a rib injury. RW Jiri Hudler was scratched to make room for Abdelkader, who replaced Hudler on the struggling third line with Mike Modano and Dan Cleary. ... Nashville F Linus Klasen, recalled from Milwaukee (AHL) on Friday, was in the lineup.