After taking the lead on 6 minutes through a right foot strike by Marc Richards the Cobblers left themselves a mountain to climb when falling behind to goals from Andew Tutte and a Tom Soares header right on half time.
Opponents Bury continued to dominate and went further ahead on 57 minutes through Danny Mayor.
The game boiled over midway through the half when Cobblers Ivan Toney and Shakers Hayden White were sent off for fighting.
Chris Hackett's long range shot with 13 minutes to go gave Northampton a boost but in the end it was not enough to avoid another narrow defeat.
Cobblers are 19th in the table and five points clear of the two relegation spots with manager Chris Wilder admitting to BBC Radio Northampton afterwards that his side need 'a point from somewhere' to arrest their current slide.
Sixfields attendance was 4563.