Marco Gabbiadini's first hat-trick in a Northampton shirt sealed Colchester's fate.
The journeyman striker notched a classic treble, one with his left foot, one with his right, sandwiching a header in between, as the Cobblers almost doubled their goal tally for the season in one night.
By contrast, Colchester fell apart despite the fact they had conceded only two goals in their last four league matches.
Gabbiadini set the ball rolling in the 15th minute when he charged down a goal kick by Richard McKinney and hooked home a left-foot shot from 18 yards.
The Cobblers increased their lead in the 23rd minute when Jerry Gill crossed from the left and French striker Armand One netted with a glancing header at the near post.
The visitors were dragged back into the contest 13 minutes later when Ian Sampson could only turn a Micky Stockwell cross into his own net but Gabbiadini restored the home side's two-goal advantage in first-half injury time with a close-range header.
Northampton could have piled on even more agony after the break with Paul McGregor striking the crossbar but Gabbiadini completed his hat-trick with a right-foot drive after latching onto an One pass in the 61st minute.
Home boss Kevan Broadhurst said after the match: "Marco still has good qualities but he's 34 now and you have to remember we play a lot of games.
"But I thought his third goal was a top quality finish and on another day he could have had four or five."
Broadhurst added: "We started very well with a good tempo and were pressing the ball. I was disappointed we didn't score earlier than we did."
Dejected Colchester manager Steve Whitton said: "That's as bad as we've defended all season. They started very sharply, got the early goal and then had the confidence to go on. That drained us and we were always chasing the game."
Whitton added: "It's fair to say their two front lads got the better of our defenders. My players have not done themselves justice."