Colin Daniel grabbed the only goal of the game as Macclesfield sent Northampton crashing to their fourth straight defeat.
The winner came early in the second half but was no more than the visitors deserved after they held the upper hand throughout the contest.
The result leaves Northampton without a victory in the last 10 games and looking over their shoulders at the relegation zone.
Macclesfield dominated the first half with Tyrone Barnett denied by Chris Dunn and then having a goalbound shot blocked by Marcus Hall. At the other end, Jose Veiga saved bravely at John Johnson's feet but then saw Shaun Harrad flash a shot wide following an error from Paul Morgan.
Harrad then volleyed wide at the far post but Macclesfield made the breakthrough nine minutes after the restart when Sam Wedgebury's cross was only partially cleared and Daniel drove home from the edge of the bar.
Veiga tipped over a dipping free-kick from Josh Walker on the hour but Wedgebury should have doubled Macclesfield's lead six minutes later only for Dunn save at his feet after he raced clear.
Veiga produced a fingertip save in the 70th minute to keep out an Andy Holt header and Harrad could only fire the rebound into the side-netting.