The win was no more than they deserved after seeing off a dreadful Sheffield Wednesday side.
The Owls look like relegation fodder and they will have to improve remarkably if they are to clamber away from the drop zone. They were a distant second best against their super-confident hosts.
Colchester deservedly went into the lead in the 28th minute, thanks to Jamie Cureton's 150th career league goal. The U's striker chased a long ball and managed to nip in between defender Madjid Bougherra and keeper Bradley Jones to lob into an empty net.
The U's were good value for their 1-0 half-time lead, but Wednesday had one great chance to equalise on 54 minutes. That proved a turning point.
Owls striker Steven MacLean pounced onto a pass by Yoann Folly, only to scoop his shot over the bar with just keeper Aidan Davison to beat from six yards out.
It was a terrible miss from MacLean, and he and his team-mates were made to pay just two minutes later as Greg Halford blasted Colchester into a two-goal lead.
It was a stunning strike from an on-song Halford. The U's right-back let fly from 30 yards out with a real screamer that flew into the roof of the net, via the far post. It was his second of the season.
Wednesday were rocking, and they were effectively killed off by Chris Iwelumo's shot from the edge of the box just after the hour mark. The big Scotsman latched onto Richard Garcia's throughball before giving poor keeper Jones no chance.
Jones had little chance with any of Colchester's goals. That was the case again with six minutes remaining when U's skipper Karl Duguid capped a fine evening for his side by drilling home a spectacular fourth goal.
The U's kept going right to the end, determined to keep a clean sheet as well, and they achieved that thanks to Davison's brilliant stoppage-time save. He tipped Folly's goal-bound shot over the bar in spectacular fashion.
Colchester have now suffered just one defeat in their last eight matches, a marvellous record considering that they lost their first five League and Cup fixtures this season.