Northampton suffered their first home league defeat since early September after they were thrashed 4-0 by play-off chasing Colchester.
Frank Nouble's close-range finish set United on their way before a three-goal blitz in the second half clinched just a second win in eight games for John McGreal's men.
Cobblers debutant Marvin Sordell poked wide of an open goal early on but it was all Colchester thereafter, Nouble giving them the lead when turning in Harry Pell's header in the 25th minute.
Pell then saw a goal-bound shot blocked by Charlie Goode before United made their superiority tell in a rampaging second half performance.
They struck twice in three minutes as Sammie Szmodics teed up new signing Abobaker Eisa to make it 2-0 shortly after half-time.
Eisa then turned provider with Kane Vincent-Young smashing home a third, and Colchester had another on 66 minutes when Brennan Dickenson squared for the impressive Szmodics to slot past David Cornell.
United should have inflicted more misery on their hosts too when awarded a late penalty, but Cornell kept out Pell's weak spot-kick.