Despite 18 places separating the two teams in the table, it was fourth-from-bottom Alfreton who went in front in the sixth minute. After Andy Halls had committed a foul inside the area, Bradley Wood stepped up to put away the resulting spot kick.
However, 11 minutes later, Macclesfield got back on level terms through Matthew Barnes-Homer, who ran clear of the defence before slotting home his four goal of the season.
The equaliser handed Macclesfield the momentum, and after Barnes-Homer had driven wide and George Pilkington had seen a header cleared off the line, they edged in front shortly before the half-hour mark.
A mix-up in the Alfreton defence allowed Waide Fairhurst to move forward before playing the ball to Barnes-Homer to net his second of the match from close range.
With nine minutes of the half remaining, Danny Whitaker made it three when he scored his third of the campaign with a 25-yard strike to put his side in full control at the break.