Substitute Paul Connor's late winner for Orient moved the London club three points clear of the relegation zone.
Matt Lockwood, Luke Guttridge and Gary Alexander all went close for Orient and just after the restart Wayne Corden's free-kick was well saved by Mark Bunn.
Orient keeper Glyn Garner did equally well to foil Ryan Gilligan and then Scott McGleish from close range.
And with 11 minutes to go Bunn failed to hold on to the ball, allowing Connor to sweep the ball home.
Northampton: Bunn, Chambers, Dyche, Doig, Bojic (Bradley Johnson 56), Holt, Hunt (Wright 74), Gilligan (Kirk 83), Burnell, Jess, McGleish.
Subs Not Used: Dunn, Quinn.
Booked: Hunt, Gilligan.
Leyton Orient: Garner, Miller, Mackie, Saah, Lockwood, Chambers, Guttridge, Easton, Corden (Tudor 59), Alexander, Walker (Connor 74).
Subs Not Used: Barnard, Keith, Morris.
Booked: Easton, Garner.
Goals: Connor 79.
Att: 4,728.
Ref: A Taylor (Cheshire).