Visiting Dons rarely threatened to spoil the party, although the home side didn't grab their second until the last minute of stoppage time.
The U's began brightly and Neil Danns fired them in front on 13 minutes. Midfielder Kevin Watson was the creator with an inch perfect pass for Danns to run onto and drill a shot past keeper Matt Baker from 15 yards out.
It was Danns' fifth goal of the season and it was a good way to bounce back for the former Blackburn man as he had missed a late penalty at Swansea last weekend.
Colchester had countless chances to score a second early in the second half, but they were denied by some excellent saves from the impressive Baker.
Greg Halford's goal bound free-kick was well blocked by Baker and the Dons keeper recovered well to also save the follow up header by Chris Iwelumo.
Both Jamie Cureton and Mark Yeates also went close, but the Dons came more into it during the latter stages, after being reduced to ten men. Their skipper Ben Chorley was sent off for foul and abusive language by Paul Millen in the 61st minute and despite the numerical advantage, the U's struggled for a while.
Sam Stockley had a vital block to deny Stephen Quinn in the danger area, but the U's weathered the storm and grabbed a second with virtually the last kick of the game.
Sub Richard Garcia was pulled down by Baker resulting in a penalty and a booking for the visiting keeper. Up stepped Colchester's leading marksman Iwelumo to convert his 13th of the season.
The Essex club are now up to fourth in the League One table while the Dons continue to struggle at the other end of the table.
The U's are unbeaten in their last 11.