Saints secured third place in the Super League with the victory, which came thanks to tries from James Roby, Tommy Makinson, Andrew Dixon, Josh Jones and Jonny Lomax.
Wigan were reduced to 12 men after forward Michael McIlorum was dismissed for a late hit on Saints prop Anthony Laffranchi - a moment that had a serious bearing on the high-octane derby.
With a man less after just 14 minutes, the Warriors were always fighting an uphill battle and, despite tries from Thomas Leuluai, Pat Richards and Sam Tomkins, they could not muster enough to topple the visitors.
"I don't think the referee got it right," said Wigan coach Shaun Wane. "It looked like Micky Mac was committed. He's an important player and I want him playing for me next week. We'll go there and fight it if we have to. We feel we have a strong case.
"Leaving your team-mates in a massive game against your arch rivals is like a suspension in itself. I don't mind the sending-off if they are consistent through the year."
St Helens interim coach Mike Rush said: "It's always going to be talking point or a turning point. They had to work a bit harder but they are still a very good side. They still threw an awful lot at us and we had to defend really well."