Wigan ran in five tries as they eased to a comfortable win over St Helens on their first trip to Langtree Park.
After Francis Meli's early score, Wigan turned it round by the break through Darrell Goulding and George Carmont.
Sia Soliola then responded after the restart to pull it back to 12-10.
But Wigan finished strongly, midweek tonsillitis victim Sam Tomkins scoring before Michael Shenton's sinbinning triggered two further late Wigan scores from Gareth Hock and Jeff Lima.
Playing their first game since the announcement of coach Nathan Brown's end-of-season arrival, Saints badly missed suspended duo Paul Wellens and Adam Laffranchi.
And, although on a high after back-to-back triumphs over Leeds and Warrington under caretaker coaching team Mike Rush and Keiron Cunningham, they never recovered from the shock of losing scrum-half Jonny Lomax with a badly-broken finger after just 16 minutes.
But the Warriors had to overcome the absence of five first-choice forwards, skipper Sean O'Loughlin, Epalahame Lauaki, Lee Mossop, Ben Flower and Liam Farrell. And coach Shaun Wane revealed afterwards that full-back Tomkins had been unable to train all week because of tonsillitis and had only played because it was the derby.
It was Tomkins' uncharacteristically clumsy loss of the ball in the tackle that allowed Meli in at the corner to open the scoring on nine minutes.
But, if that was a surprise, it was nothing compared to the shock of seeing a loose pass by James Roby in the move that sparked Wigan's 16th-minute response, Goulding racing away for his sixth try of the season.
Josh Charnley, again deputising as kicker with Pat Richards nursing the effects of his existing thigh injury, kicked the goal. And he was again successful with the boot when Carmont claimed Wigan's second try on 26 minutes.
With Lomax's loss countered by the withdrawal of one of Wigan's key men Richards, that earned the Warriors a 12-4 interval lead, which could have been more but for Soliola's superb last-ditch smother tackle to deny youngster Jack Hughes a try right on the half-time hooter.
That was made to look potentially even more important when Soliola capped a spell of sustained Saints pressure by crashing over 11 minutes into the second half, Makinson adding the extras.
But, eight minutes later, Wigan were able to restore their eight-point cushion when a superb offload by Hock allowed the artful Tomkins to sidestep his way over.
Tomkins rubbed it in with a gleeful victory dance in front of the home fans, who had cause to feel doubly aggrieved as Hock had not been pulled up for a double infringement at the previous play-the-ball.
Wigan then had cause to feel aggrieved themselves when Goulding was denied a second try late on by Shenton's deliberate off-the-ball obstruction.
Shenton was duly sinbinned, forcing Saints to spend the last 10 minutes down to 12 men.
But, although Wigan were still disappointed that the officials did not deem it worthy of a penalty try, they quickly made up for it when the excellent Hock went over for try number four.
Hock tarnished his performance by throwing the ball into the Saints fans to celebrate his fourth try in five games, earning a rebuke from referee Phil Bentham.
And Lima took further advantage of the extra man to claim another under the posts just five minutes later, Charnley adding his fourth kick.
Saints then also lost England forward Jon Wilkin with a shoulder injury just before the end to cap a miserable afternoon as Rush and Cunningham suffered their first defeat.
FROM THE DRESSING ROOM
St Helens interim coach Mike Rush told BBC Radio Merseyside:
"I can't fault any of our players for their effort and their enthusiasm.
"We had to defend large numbers of sets in the first half and it probably hurt us more than we thought at half-time.
"We came out after half-time and I thought, for 10 or 15 minutes, we had them.
"At 12-10, if we're next to score, I'm pretty sure it would have been a different result."
Wigan Warriors coach Shaun Wane told BBC Radio Manchester:
"I'm not grumpy today, I'm the happiest man in the North West.
"I thought the character we showed was outstanding and to come up with a win like that was outstanding.
There were some outstanding individual performances, but as a team we showed toughness and character.
"To come here in the first derby match here and win, it's the best feeling in the world."
GOOD FRIDAY LINE-UPS
St Helens: Makinson; Gardner, Shenton, J Jones, Meli; Hohaia, Lomax; Perry, Roby, Magennis, Flannery, Puletua, Wilkin.
Replacements: Soliola, McCarthy-Scarsbrook, Flanagan, Clough.
Wigan: S Tomkins; Charnley, Goulding, Carmont, Richards; Finch, Leuluai; Prescott, McIlorum, Lima, Hock, Hansen, Tuson.
Replacements: Dudson, Hughes, L Tomkins, Spencer.
Referee: Phil Bentham (Warrington).