The homeside thought they had taken the lead on 23 minutes when big Jon Parkin bundled both the ball and opposition keeper Paul Musselwhite into the net only for the referee to disallow the goal on the ruling of his assistant.
Scunthorpe carved out the opener on 29 minutes when the impressive Andy Keogh found Matt Sparrow with a slide rule pass, the right winger flying into the box before lashing home a low drive into the far corner.
Macclesfield equalised on the stroke of half time, the jinking Danny Whittaker picking out Paul Harsley with a neat pass across the six yard line for the midfield man to drill home.
Scunthorpe were again the better side after the break, Lee Ridley in acres of space skewing a shot across the face of goal where Paul Hayes bagged an opportunist strike.
Both Mike Sheron and Danny Whittaker both went close for Macclesfield with Richard Kell fizzing a drive inches wide at the upright for Scunthorpe.
Macclesfield then earned a controversial penalty as Nathan Stanton was judged to have barged Parkin in the box, Matthew Tipton duly stepping up to lash home his second goal of the season from the spot.
Sheron then forced a superb save from Musselwhite, but it was Hayes who might have stolen the game deep into injury time when a low shot cannoned off the upright.