Wigan survived a first half, during which Hull asked them all manner of searching questions, to gain convincing revenge for their Challenge Cup defeat two years ago.
Only a combination of hard defensive work and opportunism put Wigan in front at the break, but they took control after that with their scrum-half, Adrian Lam, scoring a try to ensure them a place in the fifth-round draw.
The first half was a strange affair, dominated territorially by Hull, but started and finished by a Wigan try.
A quick penalty taken by Julian O'Neill helped to set up the first score. Terry O'Connor sustained the momentum and, when David Furner was stopped on the line, Terry Newton demonstrated his familiar ability to force his way over the try line from close range. Andy Farrell added the goal, but Wigan found themselves under pressure from most of the rest of the half.
Jason Smith was the dominant figure for Hull, probing relentlessly for a way through the Wigan defence but never being quite able to find one.
As half time approached, it looked as though that pressure may pay off, but their substitute Paul King threw out a loose pass which was picked off by Farrell. He had the presence of mind to slip the ball out of a two-man tackle to Gary Connolly who was back from rugby union to show that he still has enough of his old pace to get around the outside of Dion Bird for the second Wigan try.
Smith finally engineered the breakthrough two minutes into the second half, an extraordinary reverse pass allowing Graham Mackay to force the ball on to the whitewash. Matt Crowther missed an easy kick to leave his side two scores behind.
They soon slipped further behind, allowing the young Wigan substitute Steven Wild to weave through a series of tackles for his first senior try. With Smith missing a key phase of the game in the blood-bin, Hull suddenly looked a spent force and, four minutes later, Lam took a pass from Newton and sold a dummy to dart over the line.
Kris Radlinski managed to pounce on Lam's kick just before the dead-ball line as Wigan stretched clear. Smith's short pass sent Garreth Carvell over, but Hull had let the game get too far away from them and, in the last minute, the Kiwi prop, Craig Smith, marked his Wigan debut with a try.
Wigan: Radlinski, Carney, Connolly, Ainscough, Dallas, O'Neill, Lam, O'Connor, Newton, C Smith, Cassidy, Furner, Farrell. Substitutes used: Howard, Johnson, Wild, Bibey.
Hull: Bird, Raynor, Kohe-Love, Mackay, Crowther, Chester, Horne, Greenhill, Jackson, Craven, Maher, Ryan, J Smith. Substitutes used: King, Carvell, Cooke, Parker.
Referee: S Cummins (Widnes)