Jordi Gomez's penalty just seven minutes in was enough for Roberto Martinez's side to book their place in the fifth round.
Macclesfield had a penalty shout turned down in each half by referee Roger East in a battling performance which saw them unable to convert any of their chances against the Premier League side ranked 82 places above them.
It was Macclesfield's first time in the fourth round in their entire history, and what the Blue Square Bet Premier side lacked in invention they replaced with physicality in the early stages.
However, it was the pacier Premier League outfit who took an early lead following some clumsy defending by the home side. Gomez passed the ball to Callum McManaman as he raced down the left and looked to dink through the Macclesfield defence, only to be brought down by Thierry Audel for a penalty.
Gomez stepped up to take the resulting spot-kick and fired it just out of reach of Macclesfield keeper Joe Anyon, who got his fingertips to the ball with his first touch for his new club having only joined this week.
As Macclesfield began to settle into the game their confidence grew, with several breaks and shots making it unclear to the casual observer which side was the team in the top flight.
Macclesfield's best chance of the first half came after Waide Fairhurst's penalty shout was waved away by the referee, with Audel almost atoning for his earlier error with a headed effort saved on the line from the resulting corner by John Paul Kissock.
Wigan almost doubled their lead straight from the kick-off when Nouha Dicko raced into the Macclesfield box, but Anyon made a terrific save to keep his team in the tie.
Macclesfield, who knocked out Championship leaders Cardiff in the previous round, kept up the pressure on Martinez's side, but a late corner by substitute Peter Winn did little to create any problems in the Wigan box as the clock ticked down.
Wigan looked to have escaped a penalty against them after what appeared to be handball from David Jones in the Macclesfield box from Ryan Jackson's cross, but again referee East waved the home side's shouts away.
The Silkmen then threw everyone forward with seconds left of normal time as Wigan put everyone but the keeper behind the ball due to wave after wave of attack from the home team.
However, there was not to be a shock for Macclesfield, who were the lowest ranked team left in the competition ahead of the match, as Wigan held firm to keep their cup hopes alive.