The Latics - who saw off Crystal Palace by the same scoreline in the last round - took the lead in the 18th minute when Chris McCann slotted home after being teed up by Jordi Gomez.
Cardiff replied nine minutes later via Fraizer Campbell but Ben Watson - the man who scored the only goal in last season's final victory over Manchester City - restored the visitors' lead with a terrific strike from 30 yards five minutes before the break.
Neither side could find the net in the second period as Uwe Rosler's side held on to post another famous win.
There were several new faces for the home fans to get behind. Spanish defender Juan Cala made his debut for the club, having joined from Sevilla.
Norwegian recruits Mats Daehli and, in the absence of banned talisman Craig Bellamy, Jo Inge Berget, made their first appearances at Cardiff City Stadium.
But it was Wigan who produced the first meaningful attack when Callum McManaman latched onto a crisp cross-field ball from Watson before dragging the ball just wide of the left post.
And it was the Latics who opened the scoring in the 18th minute. When the Bluebirds failed to clear, the hustling Gomez pilfered the ball before finding McCann unmarked in the box. Manchester United loanee Wilfried Zaha showed no urgency to intercept the cross and all McCann had to do was sidefoot it home.
Watson continued to play with freedom in the centre of midfield, putting McManaman - who shifted from right to left wing early on - through before he forced a corner.
As the half wore on Premier League outfit Cardiff - and the repentant Zaha - began to impose themselves.
The 2008 FA Cup finalists' equaliser came after 27 minutes through top scorer Campbell. After a scramble in the box and two blocked Cardiff shots, he struck low and hard past the unsighted Ali Al Habsi for his third goal of the competition, and eighth of the season.
Zaha opened his box of tricks as he started to become the threat Cardiff fans had been hoping for and crossed for Campbell who headed over.
Wigan were bereft of territory and chances until centre-back Cala gave away a free-kick almost 30 yards out, five minutes before the break.
He was made to pay as Gomez shifted the ball to Watson, who cracked it sweetly past in-form goalkeeper David Marshall.
A chance for an equaliser fell for the Bluebirds on the stroke of half-time when Cala emerged from a melee in the box to head the ball against the post from a yard.
After the break, Daehli continued his impressive afternoon in the Cardiff midfield when he repeatedly cut inside from the left and tested the opposition.
City keeper Marshall was almost embarrassed when he let a wayward cross go out for a corner, only for McCann to hook the ball goalwards, forcing a reaction save.
It was Daehli again who unlocked the Latics defence when Zaha had a penalty claim turned down. The Norwegian twisted and turned before slotting a deft pass through to the winger, but referee Martin Atkinson saw a fair challenge.
A largely uneventful second half until the final 10 minutes was perfect for the visitors as they sat on their lead.
But for a couple of nervy moments - a deflected shot from Daehli and an Al Habsi save off Zaha - the Championship side looked relatively comfortable.
Bluebirds replacement Craig Noone also tested Al Habsi, forcing him to tip the ball, at full stretch, past his right-hand post but the Latics held on to make the last eight.