An opportunist effort from Simon Cox after just 12 minutes and an own goal by the luckless Aiden Palmer just before the break, pushed lifeless Orient nearer the drop zone.
Ironically, the home had made a bright start when Shane Tudor skipped down the right and sent in a cross that stand-in skipper Craig Easton just failed to reach.
But Northampton struck a deadly early blow when Justin Miller lost possession and allowed Ryan Gilligan to thread the ball neatly through to Cox, who fired home left-footed from 16 yards.
Apart from a couple of glancing headers from Gary Alexander and a fierce drive from Ryan Jarvis, Orient rarely looked like breaking down Town's stubborn defence.
Indeed, the visitors, with an impressive away record, threatened on the break as Cox sent in a snapshot, before the visitors stretched their lead on 40 minutes.
Cox was the architect with a cross shot that found Jason Crowe and his shot hit a post and went in off the unfortunate Palmer.
After the break Orient threw caution to the wind as substitute Jabo Ibehre replaced Palmer and Orient played with three out and out strikers.
The home side had a penalty appeal turned down when Jarvis was tugged by Alex Pearce and then the same player rattled the bar with an acrobatic overhead kick.
But Northampton weathered the storm and comfortably saw out six minutes of stoppage time to emerge as worthy winners with a thoroughly professional performance.