Cardinals manager Tony La Russa, fresh from a five-game World Series victory over the Tigers, dropped the ceremonial first puck. It failed to spur the Blues, who have lost eight of nine to the Red Wings the last two seasons.
Bill Guerin scored his fourth goal on a deflection in the second period for the Blues, who played their first game in a week. Radek Dvorak's short-handed breakaway cut the gap to one with 3:26 to go.
Detroit played for the second straight night after winning 5-4 at Dallas on Friday.
Red Wings backup goalie Chris Osgood, formerly with the Blues, outplayed Manny Legace, who joined St. Louis as a free agent in the off-season. Osgood got a pair of friendly bounces midway through the third period when Dennis Wideman's wrist shot deflected off both goal posts with Detroit leading 3-1.
The goal light went on but replays indicated the puck did not cross the line.
Holmstrom scored on the Red Wings' first shot at 4:33 of the first, scoring the 300th point of his career. His second goal came on a second-chance deflection at 6:34 of the third.
Legace stopped the initial attempt but Holmstrom batted in the puck for his third goal of the season.
The Red Wings also converted their second shot of the game, with Valtteri Filppula split defenders and flipped in a backhander at 6:32 of the first for a 2-0 lead.
Notes: D Christian Backman, playing his first game of the season after off-season shoulder surgery, assisted on Guerin's goal. ... The Blues have been tied or trailed by one goal in the third period of all nine of their games. ... Datsyuk has two goals and four assists in his last four games. ... This was the first of eight games between the teams.