Wigan suffered their first Magic Weekend defeat since 2008 as they failed to put their Super League campaign back on track.
Joe Burgess' try early in the second-half had locked the score 8-8 and raised hopes of victory - in their third meeting with Warrington this season.
But a rapid-fire salvo from Blake Austin and Toby King midway through the second-half swung the game in Wire's favour.
And with Dec Patton masterful with the boot, striking seven goals from as many attempts, it ensured the revived Locker Cup would be heading to the HJ Stadium.
Wigan's performance was a step up on the previous week but that was little comfort after another loss - and with familiar flaws and shortfalls present and accounted for.
They trailed 8-2 at half-time and though they had a bright spell early in the second-half, they were well beaten in the three-tries-to-two loss.
In the headlining game of the Magic Weekend's opening day, Anfield rocked with thousands of Wigan and Warrington fans among the healthy opening day attendance of 30,057.
Organisers again did a splendid job with the annual carnival, with stalls and activities outside the ground and events between matches to keep the day flowing quickly.
While England were here last autumn, this was Wigan's first appearance at the home of Liverpool FC since they beat Penrith in the 1991 World Club Challenge.
Adrian Lam - whose mum was raised in a street just across Stanley Park - was disappointed with their no-show at the Nou Camp and hoped for a better show, though he wasn't helped by injuries.
Thomas Leuluai, Sam Powell, Romain Navarrete and Liam Marshall were all forced out of their side beaten 33-16 by Catalans.
In their place, Jake Shorrocks, Jarrod Sammut, Morgan Smithies and Oliver Partington returned.
Chris Hankinson was chosen to fill the right wing role, while Sean O'Loughlin started at half-back.
With both teams playing in stylish retro shirts to mark the 30th anniversary of their clash in Milwaukee, USA, they went set-for-set from the start as they settled into the contest.
Zak Hardaker, one of their better players, broke the deadlock with a 15th minute penalty. But their lead didn't last long as Tom Lineham smartly kicked on for Patton to score Wire's opening try, which he converted.
And Wigan's woes deepened when Joe Greenwood was injured from the restart, forcing him off the pitch for a second successive week.
Wigan worked hard to try and shut down Wire's main attacking threats, Bake Austin and Daryl Clark, and in a gritted defensive performance there were some notable contributions from Tony Clubb and Hardaker.
They appeared to be holding their own, but with the ball they appeared disorganised and even though they put plenty of width on the ball, they rarely troubled the Wolves.
Errors crept into Wigan's display and Patton poked Wire 8-2 ahead before the break.
But they started the second-half with a little more intent and direction, Burgess finishing off an early attack as he squeezed over in the corner. Hardaker couldn't convert, but he struck a subsequent penalty to lock the scores after a spell of pressure from the Warriors.
Wigan appeared on the ascendancy but when Taulima Tautai released the ball in a tackle to clutch a neck injury, he was pinged for a knock-on and - from that spell - the Wolves retook the lead with a sprinkling of magic from leading Steve Prescott Man of Steel candidate Austin.
The marquee No.6 angled inside and attacked the defence, powering beyond three flapping defenders on the way to the line to make it 14-8 by the hour-mark.
Lam's side recovered and pressed for a leveller - only to be struck by a cruel sucker-punch, as Josh Charnley gobbled up a loose ball and released King to the line.
Patton hit the conversion and a penalty moments later opened up a three-score lead with 15 minutes to go.
Wigan didn't give up and with five minutes to go, O'Loughlin put Willie Isa through an opening before Hardaker's conversion reeled in the Wolves' lead to 10 points - only for Patton to hit another penalty to swell the scoreline.
They take a break next weekend for the Challenge Cup before returning to league action with an away game at Hull KR.
Wigan: Hardaker; Hankinson, Sarginson, Gildart, Burgess; Williams, O'Loughlin; Flower, Shorrocks, Bullock, Isa, Greenwood, Clubb. Subs: Tautai, Smithies, Sammut, Partington.
Warrington: Mamo; Lineham, Goodwin, King, Charnley; Austin, Patton; Hill, Clark, Cooper, Currie, Hughes, Philbin. Subs: Tautai, Smithies, Sammut, Partington.
Referee: Chris Kendall