Wigan manager Roberto Martinez made seven changes, but his side was still too good for Huddersfield and cruised through to the FA Cup quarter-finals for the first time in 26 years.
Winger Callum McManaman and midfielder James McArthur were two players Martinez recalled and they rewarded the Spaniard with displays full of Premier League class.
McManaman struck a fine opening goal in the 31st minute and Arouna Kone tapped home a second shortly before the break to leave new Huddersfield manager Mark Robins with a difficult half-time team-talk in his first match in charge.
McArthur struck a brilliant third goal from the edge of the penalty area early in the second half and although Huddersfield substitute Lee Novak headed home just after the hour, it was not enough to trouble Wigan .
The visitors soaked up a fair portion of late pressure but emphatically underlined their superiority when Kone thundered home a fourth goal in the closing stages.
Home fans were hoping Huddersfield Giants' Super League win over Wigan Warriors yesterday on the same pitch was a good omen.
What was apparent from kick-off was a bobbly playing surface, but Wigan settled quicker and Jordi Gomez headed an early cross from McManaman over the bar.
Wigan dominated early possession, but Huddersfield carved out their first chance of the game when Alan Lee failed to keep his header on target from Calum Woods' cross.
McManaman rolled an inviting ball across the six-yard box at the other end in the 25th minute, just out of Kone's reach, but Wigan took the lead six minutes later with a goal stamped with top-flight quality.
McArthur swivelled on the spot and sent a fine ball in behind Huddersfield right-back Jack Hunt to set McManaman free and the Wigan winger raced into the penalty area before dinking a cool finish over sprawling home goalkeeper Alex Smithies.
Huddersfield were unable to hurt their opposition and Wigan doubled their lead five minutes before half-time, with McManaman this time the provider.
The wide man's pace again sent him clear of Hunt and his excellent low cross was met by Gomez, whose goalbound shot was blocked only for Kone to flick home the rebound at the far post.
Town strikers James Vaughan and Lee Novak replaced Lee and Chris Atkinson during the break and the latter almost cashed in on a defensive mix-up soon after, but his shot was well blocked by Wigan goalkeeper Joel Robles.
Normal service was soon resumed though. McManaman won another race to the by-line and his subsequent cross caused more panic in the home rearguard.
Maynor Figueroa then burst into the Huddersfield area and unleashed a shot into the side-netting before McManaman and McArthur combined on the left again to put the tie beyond doubt in the 56th minute.
This time McArthur received the telling pass and from the edge of the area he arrowed an unstoppable shot beyond Smithies into the top corner.
But Huddersfield did not lie down and Novak lifted home spirits when heading home Woods' pinpoint cross six minutes later.
The Town substitute just failed to latch on to a ball over the top and the Yorkshire side did mount a late rally, but a smart Robles save from Neil Danns' late cross snuffed out once chance and Wigan soon added a fourth.
Kone pounced on a loose ball 25 yards from goal in the 89th minute and after evading the covering defence crashed home a right-footed shot from just inside the area into the roof of the net.