Despite a promising first 45 minutes for the hosts, goals from Rod McDonald and Ricky Holmes gave the Cobblers the advantage before James Collins added two late goals to seal the win.
Having secured an impressive win at Portsmouth the week before, O’s player-manager Kevin Nolan stuck with the same XI for the visit of Northampton.
There were two changes on the substitutes bench however as Charlie Grainger and Nigel Atangana returned to the squad having missed the trip to Fratton Park.
In Baltic conditions the O’s lined up in a 4-1-4-1 formation which saw Jack Payne sit just in front of the back four.
The hosts who enjoyed the majority of possession during the opening exchanges, though Northampton had the first chance of the afternoon when James Collins volleyed Ricky Holmes’ cross into the side netting.
Following Collins’ chance Orient continued to have a lot of the ball, and two neat moves saw Cobblers’ goalkeeper Adam Smith first hold a Kevin Nolan flick before getting down low to smother Jobi McAnuff’s drilled shot from inside the area.
With just over 30 minutes played Frazer Shaw combined well with Calaum Jahraldo-Martin down the left before delivering a low ball into the path of top scorer Jay Simpson. Although the striker was unable to get a shot away Nolan and then Sammy Moore had shots well blocked by the opposing defence.
As the half time whistle loomed Rod McDonald sent a header over for the visitors, but that was the final chance of the half as the sides went into the break all square.
Both sides returned for the second half unchanged, and following a tight start Northampton made the breakthrough on the 55th minute when centre half McDonald acrobatically fired an overhead kick beyond the reach of O’s goalkeeper Alex Cisak and into the far corner.
Having taken the lead the Cobblers then continued to control the ensuing minutes before doubling their advantage through a moment of individual brilliance when Ricky Holmes picked the ball up 20-yards out before unleashing a volley just under the crossbar.
Striker Armand Gnanduillet was then brought on in place of Jahraldo-Martin in response to the goal, as Orient reverted to a flat 4-4-2 in a bid to find a way back into the game.
The change in formation saw McAnuff switch to the left of midfield, and with just under 20 minutes remaining the 34-year-old picked out the run of Gnanduillet with a fantastic pass but the substitute could only drag his shot wide as Nolan desperately tried to get a telling touch.
As the hosts continued to up the pressure Simpson then came a whisker away from pulling a goal back when Shaw’s cross from the left eventually fell to him in the box, but despite turning well could only watch as his shot curled the wrong side of the post.
Despite the O's creating several chances the game was put to bed six minutes from time when Cobblers striker Collins made it three for the visitors with a close range finish following a corner.
Collins was to then claim a second in stoppage time when a swift counter attack concluded with the striker drilling a shot beyond the dive of Cisak.
ORIENT: Cisak, Hunt, Baudry (C), Brisley, Shaw, Payne (Palmer 85), McAnuff, Moore (Pritchard 78), Nolan, Jahraldo-Martin (Gnanduillet 67), Simpson
SUBS: Grainger, Essam, Clohessy, Atangana
NORTHAMPTON: Smith, Moloney, Diamond, McDonald, Buchanan, Holmes (Taylor 81), O’Toole, Rose, Martin (D’Ath 65), Collins, Richards (Cresswell 87)
SUBS: Clarke, Adams, Prosser, Hoskins
GOALS: McDonald (55), Holmes (64), Collins (84 & 90+1)
BOOKINGS: Martin (33)
REFEREE: Paul Tierney
ATTENDANCE: 6,131 (1,135)