Despite missing six regulars through injury and suspension, Paul Peschisolido's side twice came from behind before Sam Winnall fired home an 89th-minute winner from the penalty spot - leaving Town stunned after they had taken a 2-1 lead in only the 81st minute.
Macclesfield made a blistering start, opening the scoring inside 22 seconds as Emile Sinclair pounced on Tyrone Barnett`s pass to score from close range.
There could have been more goals in a frantic start but Burton pair Greg Pearson and Ryan Austin were both denied on the line, while Sinclair fluffed a gilt-edged chance for the Silkmen from six yards.
As Burton battled for the equaliser Winnall shook the crossbar with a free-kick from the edge of the area in the 26th minute.
But Calvin Zola did put the home side back on level terms three minutes before the break when he pounced on a rebound to drill home a right-footed shot from the edge of the area.
However, the visitors looked to have secured the points when they regained the lead nine minutes from time, Barnett's cross tailor-made for the unmarked Sinclair to head home from six yards.
But the hosts hit back to level for the second time when Adam Bolder headed home a Jack Dyer free-kick five minutes later.
Then Winnall stepped up to score from the spot after Jacques Maghoma had been tripped by Izak Reid.
Burton Albion 3-2 Macclesfield: Match Report - view commentary, squad, and statictics of the game as it happened.