The Premier League side rode their luck at times but showed more ruthlessness in front of goal to advance.
It did not take Wigan long to show their superiority when youngster Callum McManaman was brought down after finding space in the box. Jordi Gomez stepped up and scored the penalty, despite Joe Anyon getting a good hand to it.
They nearly doubled their lead soon after when a good cross from Ronnie Stam found McManaman free in the area again. This time though, the winger turned away from his marker but could only shoot wide.
Macclesfield began to dominate after that, particularly down the right side through Jack Mackreth. One of his many crosses found its way to top-scorer Matthew Barnes-Homer, but the striker's shot was saved easily.
Shortly afterwards Macclesfield had a penalty shout turned down, before Thierry Audel headed the ball straight to Joel Robles from point-blank range.
In the first minute of the second half Wigan were denied the chance to double their lead, when a good save from Anyon stopped Nouha Dicko's shot.
After that though, the home side regained the ascendancy. Keiran Murtagh had the ball nicked off his toes just as he was about to shoot from 12 yards out, before a Mackreth run into the box brought a comfortable save from Robles.
Macclesfield seemed to run out of steam in the closing stages, and despite continuing to dominate the ball, they failed to create any clear chances as Wigan edged through to the fifth round.