Larkin made it 3-0 at 5:12 of the second period when he tapped in a centering pass into the crease from Kane during a 4-on-3 power play.
Perron pushed it to 4-0 at 6:41 when he one-timed a setup into the slot from Andrew Copp by Markstrom's blocker.
"I thought we started the game really good," Markstrom said. "We really pushed them back. Obviously, they got two goals at the end of the first and then two goals early in the second.
"I saw all four pucks go in. It's frustrating. You want to be there for the guys and the fans that paid money to come watch us play."
Markstrom, who entered with a 4-1-0 with a 1.41 goals-against average and .956 save percentage in his previous five starts, was replaced by Vladar after the goal.
“It was 4-0 at that point, so nothing on Jacob; I think we can all probably agree on that,” Flames coach Ryan Huska said. “I was just trying to change the way the game was going.”
Raymond beat Vladar with a wrist shot at 15:40 of the third period for the 5-0 final.
NOTES: Kane needs one assist to become the third U.S.-born player with 800 in his NHL career, following Phil Housley (894) and Mike Modano (813). ... Detroit is 23-2-3 this season when scoring at least four goals. … The Red Wings are the fifth team Reimer has recorded multiple shutouts (Toronto Maple Leafs, San Jose Sharks, Florida Panthers, Carolina Hurricanes). … Seider and Detroit defenseman Ben Chiarot each blocked five shots, and Calgary defenseman Chris Tanev blocked six.