The rout started as early as the 42nd second when Adam Stansfield was on hand to volley home from six yards after Richard Logan had thumped the cross bar from close range.
Macclesfield striker Francis Green nearly replied in the 12th minute, but though his lob beat keeper Paul Jones, it was cleared in the six yard box by Grecians' skipper Daniel Seabourne.
The visitors extended their lead on the 33rd minute when Rob Edwards produced a slide rule pass for Ryan Harley to glide into the box before picking out the far corner with a perfect left-foot shot.
Macclesfield were handed a lifeline on the stroke of half-time when diminutive veteran striker Simon Yeo muscled Matthew Taylor off the ball before blasting home his fourth of the season from the edge of the box.
However, Exeter restored their two-goal margin just three minutes after the break when Harley picked out Stansfield, who flicked the ball off the outside of his boot into the far corner with keeper Jonny Brain transfixed to the spot.
Macclesfield twice hit the crossbar in the closing stages with substitute Martin Gritton heading a Green cross onto the woodwork, before Green saw a point-blank shot cleared off the line in the 80th minute for Yeo to crash the ball off the crossbar from six yards.
They were made to pay in the 84th minute when Grecians skipper Matt Gill was picked out by substitute Ben Watson, before lifting the ball over the keeper from a narrow angle to find the far corner.