Plucky Swindon twice came from behind to force equalisers, but in the end they fell just short in the 72nd minute when David Perkins sealed the points for the Essex hosts.
Clive Platt had taken just 108 seconds to score the winner at Oldham on Saturday and he took even less time to break the deadlock against Swindon.
Former MK Dons striker Platt volleyed home an excellent cross from Simon Hackney with just 48 seconds on the clock.
Colchester have not ruled out a late surge for the play-offs and they should have been out of sight long before Swindon scored their first equaliser.
Dean Hammond blasted a good shot over the top while livewire winger Hackney peppered the target with a couple of low shots.
But Swindon made them pay for these missed chances in the 38th minute. Striker Billy Paynter was hacked down by defender Chris Coyne for a clear-cut penalty and up stepped leading scorer Simon Cox to convert the spot-kick, sending keeper Mark Cousins the wrong way.
It was Cox's 20th goal in all competitions this season.
The U's restored their lead in the last minute of the first half thanks to another pinpoint header from Platt.
Swindon keeper Petr Brezovan could not fully clear the deflected cross and when Kemal Izzet lifted the ball back into the danger zone, there was Platt to direct his header into an empty net.
But Swindon refused to give up and it looked like they would take a point when Hal Robson-Kanu, who is on loan from Reading, capped a strong run with a ferocious left-footed shot that beat Cousins all ends up from just outside the box in the 65th minute.
However, Perkins came up with what proved to be the winner just seven minutes later.
Substitute Anthony Wordsworth did well down the left then when his low cross was only half dealt with, in swooped Perkins to crash home a shot which took a couple of deflections on its way into the net.
As a result, Swindon remain in the bottom four, while Colchester have consolidated themselves in the top ten, thanks to an unbeaten run of five games which has yielded 11 points.