Matt Peet's men looked well on course for the quarter-finals after tries from Zach Eckersley, Jai Field, Junior Nsemba and Liam Farrell took them to a 22-6 interval lead at the Brick Community Stadium on Saturday (Sunday AEDT).
Hull, who have shown plenty of fight this season under their new coach, former Australia and Penrith star John Cartwright, had only a converted try from Herman Ese'ese to show for their efforts and looked set to slide out of the competition.
But after Field limped off with a hamstring injury, the visitors rallied through tries from Amir Bourouh and Lewis Martin, who grabbed his second eight minutes from time to put his side within four of the hosts.
Australian Aidan Sezer's kick from the touchline further narrowed Wigan's advantage, and a strong spell of pressure resulted in Martin completing his hat-trick two minutes from time, bursting over in the corner from Sezer's long pass to seal a stunning win.
Elsewhere, late tries from Ben Currie and Zane Musgrove broke Widnes hearts as Cheshire neighbours Warrington fought back to claim a 26-16 win in a classic at the DCBL Stadium.
The Championship club looked the likely winners for long periods and a try from Jack Owens midway through the second half saw them dreaming of adding another chapter to their illustrious history in the competition.
Instead, Sam Burgess's men finally found a way to avoid embarrassment despite another ragged display, Currie stretching home from George Williams' kick to the corner, before Musgrove muscled over to confirm his side's place in the quarter-finals.
The win gave Burgess some welcome relief after recent big losses to Wigan and Wakefield.
"I'm happy to get the win. It wasn't perfect again, but the aim of the game is to win, so we'll take that and move on to the next one,'' Burgess said.
"No doubt we're down on confidence at the moment. There were so many great efforts out there - Ben Currie was outstanding again - and there is no doubt that winning helps."
Burgess admitted last week's high-profile signing of half-back Marc Sneyd from Salford has come at the right time, with the 34-year-old set to make his debut at St Helens on Friday.
"Sneyd offers a bit of everything and it's probably something we really lack. He's a great fit for the club,'' Burgess said.
Catalans Dragons cruised to a 46-18 win over Championship side Featherstone in Perpignan, with Nick Cotric and Sam Tomkins scoring twice in a nine-try show.
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