Cobblers went close through Kelvin Langmead's deflected header and Kemar Roofe shot straight at the experienced Mark Cousins in the United goal, as did top scorer Alex Nicholls. But Colchester had the better of the first half and created a couple of good chances. Ian Henderson tested Shane Higgs and Clinton Morrison missed a great opportunity after racing clear of the home defence.
Northampton's best chance fell to Adebayo Akinfenwa who saw his header hit the bar before Freddie Sears broke the deadlock after half an hour, superbly volleying home a right wing cross from ex-Cobbler Henderson.
Akinfenwa went close to an equaliser when he screwed his shot wide but it took a superb block from Chris Hackett to prevent Sears from doubling his tally after more good work from Henderson on the flank. The returning Higgs had to be replaced by Dean Snedker who saw another effort from Henderson deflected for a corner before he did well to foil Morrison after the restart.
But Akinfenwa equalised six minutes into the second half from the penalty spot after Roofe was upended in the box. And three minutes later Mukendi opened his account when he converted a cross from the impressive Ishmel Demontagnac.
Sears nearly levelled with another sweet volley but Nicholls went close to extending Northampton's lead after cutting into the box and he was also just off target late on. Colchester offered little in the second half and to make matters worse Morrison was sent-off in stoppage-time for a challenge on David Artell.