Jack Mackreth struck with nine minutes remaining to kill off Brackley's comeback and book Macclesfield's place in the FA Cup third round.
Danny Andrew and Scott Boden had the Skrill Premier side two goals ahead inside 50 minutes and seemingly cruising through.
Brackley hit back, though, through Steve Diggin and Owen Story only for Mackreth to shatter the Skrill North side's cup dreams at the close.
The Silkmen had started the better of the two sides and took a deserved lead when a corner was cleared only as far as Andrew, who drove into the box and smashed the ball past Billy Turley.
The game then became a scrappy affair, with Danny Whitaker firing a wild effort and Ryan Austin nearly heading past his own goalkeeper as the Silkmen chased a second before half-time.
The lead was doubled within five minutes of the restart when Andrew put Danny Rowe away and his left-wing cross was met by Boden, who tucked home his sixth goal of the season.
Brackley threw themselves a lifeline after 58 minutes when Diggin pounced after Rhys Taylor had twice denied the Saints in quick succession.
And the match was level 13 minutes later when Macclesfield failed to clear a corner and Story volleyed into the roof of the net.
But the Silkmen were back in front when Mackreth weaved his way inside two defenders and finished across the goalkeeper from a tight angle to settle matters.