Wigan, the most successful team in English rugby league, had lost the last two grand finals at Old Trafford and Declan Patton's first-half try put Warrington 6-2 ahead at the interval.
But centre Oliver Gildart and winger Josh Charnley scored tries in the second half to sink Warrington, who finished top of the Super League standings after the Super Eight stage but had not won the overall English title since 1955.
"I'm really proud of what we've done, it speaks volumes for our toughness," Wigan coach Shaun Wane told Sky Sports.
"This is best ever, an unbelievable win. The players showed so much desire. They put so many hours in, they deserve it."
(Reporting by Ed Osmond; editing by Martyn Herman)
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