Kassian gave the Oilers a 2-1 lead at 19:38, tipping a point shot by Larsson past Mrazek. David Desharnais also assisted on the goal for his first point in his debut with the Oilers. Desharnais was acquired from the Montreal Canadiens on Tuesday in exchange for defenseman Brandon Davidson.
"It's tough to play from behind against this team," Zetterberg said. "They're really skilled when they get their odd-man rushes. We were behind from the beginning, but Petr came up with some huge saves tonight."
Eberle scored at 6:58 of the third period to extend Edmonton's lead to 3-1. Eberle gained the Detroit zone, picked up the puck that bounced back to him, drove the net and took a backhand shot that beat Mrazek.
Helm made it 3-2 at 10:26, taking a long breakaway pass from Larkin and shooting through Talbot's pads.
"There are a couple of teams in the League that I know their character and leadership," said Oilers coach Todd McLellan, a former Detroit assistant. "I'm glad we're done with them. It was a tough night, not easy by any means."
Maroon scored at 14:02, taking a pass in front from Leon Draisaitl, to give Edmonton a 4-2 lead.
Larkin scored on a scramble in front with 35 seconds left and Mrazek pulled for an extra skater.