Mikel Arteta's side routed the third-tier strugglers with four goals in the first 27 minutes of the fourth round tie at the Emirates Stadium.
Noni Madueke and Gabriel Martinelli netted before Jack Hunt's own goal was followed by a Gabriel Jesus strike.
The Gunners are back in the last 16 for the first time since they won the FA Cup in 2020, a success that remains the only major trophy of Arteta's reign.
Holding a four-point lead at the top of the Premier League, through to the League Cup final against Manchester City and into the Champions League last 16, Arsenal could end their silverware drought with a remarkable quadruple this season.
Arsenal's latest FA Cup clash with Wigan lacked the drama of their previous one in 2014 - a semi-final win featuring a penalty shoot-out goal from then Gunners captain Arteta.
Wigan have fallen on hard times since, arriving in north London stuck in the League One relegation zone and led by interim boss Glenn Whelan after Ryan Lowe's recent sacking.
Arsenal defender Riccardo Calafiori was injured in the pre-match warm-up, forcing Arteta to bring Bukayo Saka back into the line-up instead of resting the England winger.
Despite the late reshuffle, it took just 11 minutes for Arsenal to go in front.
Arteta gave Eberechi Eze another start despite hauling the England midfielder off at half-time after his latest disappointing display in Thursday's 1-1 draw at Brentford.
Eze repaid Arteta's faith, cleverly turning into space for a superb pass to Madueke, who raced into the Wigan area and finished with aplomb.
Eze, signed from Crystal Palace last year, provided another assist in the 18th minute.
He guided a pin-point pass to Martinelli and the Brazilian stroked a cool finish into the far corner from 12 yards.
Arsenal's third goal arrived in the 23rd minute when Wigan defender Hunt headed Saka's cross into his own net.
Arteta's men showed no mercy as Christian Norgaard's pass sent Jesus clean through for a delicate chip over Wigan keeper Sam Tickle in the 27th minute.
Arsenal will resume their push for a first English title since 2004 at bottom of the table Wolves on Wednesday.