Mark Robins' men made a dream start on five minutes when Mark Burchill laid a perfect pass into the path of overlapping right-back Dale Tonge, who thundered home a fierce 15-yard drive from a narrow angle.
Macclesfield should have equalised on 17 minutes but from a narrow angle veteran marksman Simon Yeo lashed a simple chance off the top of the crossbar.
Yeo went close two minutes later when he forced a magnificent save from Andy Warrington with a 20-yard piledriver.
Macclesfield nearly equalised on the stroke of half-time but a looping header from Terry Dunfield floated past the far post.
The home side were again dominant in the second half and Martin Gritton missed their best chance when he glanced a free header from a pinpoint Izak Reid cross past the far post.
Rotherham looked to have sealed the game in injury time when Ian Sharps sent a looping header goalbound for it to be nodded in on the goal-line by Andrew Nicholas.
Macclesfield grabbed a consolation when Francis Green produced a stunning scissor-kick but, as James Jennings tried to grab the ball from Sharps for a quick restart, they clashed and both earned red cards for their second bookings.