Adebayo Akinfenwa, substitute Aleksander Prijovic and Ikechi Anya were the goalscoring heroes after Orient looked to be on course for victory following Jason Crowe's own goal in the first half.
In a scrappy opening it was Northampton who asserted the early pressure and they almost took the lead on 12 minutes when the dangerous Anya fired just over after Orient's Charlie Daniels did just enough to put him off.
But it was Orient who grabbed the lead on 24 minutes with their first effort on target.
Sean Thornton's wicked free-kick from the left saw Crowe send a header flashing past his own keeper Chris Dunn.
Andy Holt wasted two good opportunities to level as he first headed a cross from Luke Guttridge wide of the target and then failed to find a finish at the far post following Anya's cross.
Northampton continued to fritter chances away and Akinfenwa produced a tame shot at home keeper Jamie Jones after Anya provided the opening.
After the interval, Orient took a grip for the first time and Jimmy Smith saw a shot tipped away by Dunn before Simon Church sent a header inches wide.
But the complexion of the game changed in a deadly two-minute spell.
On 72 minutes, Akinfenwa headed home Guttridge's free-kick from the left to level things up.
Then two minutes later, substitute Prijovic made a telling contribution as he swivelled in the area and fired home a pass from Guttridge into the left-hand corner of the net.
Orient pressed hard for a leveller and Northampton Town defender Danny Jackman came to the rescue as he knocked a header from Jordan Spence off the line.
But Orient paid the price for throwing men forward when Anya caught them on the break three minutes into stoppage time and fired home a third.
The strike ensured Northampton Town of their fourth away win of the season and left them just one point from safety.