The Railwaymen completed a league double over their Essex hosts to move six points clear of the relegation zone.
A terrific run of just one defeat in eight matches has seen them pull well clear of the bottom four.
The winner arrived on 63 minutes with big striker Calvin Zola on target from close range.
Colchester have struggled to deal with set pieces all season and they again came unstuck as a long throw from Clayton Donaldson bounced inside the box and there was Zola to turn and lash home a shot at the near post.
Although there was still more than a quarter of the game, the U's rarely looked like grabbing an equaliser and in fact Crewe could have doubled their lead when Donaldson burst through on goal, only for Mark Cousins to dive bravely at his feet to save.
Earlier, Colchester dominated the first half with Crewe prepared to sit back and soak up the pressure with a five-man defence.
The visitors rode their luck at times as the U's peppered the target. Keeper John Ruddy saved well from the likes of Simon Hackney, Kemal Izzet and David Perkins and when he was finally beaten by Marc Tierney's low drive, the ball ricocheted off the far post and rolled to safety.
Colchester's cause was not helped by an injury to their winger Hackney, who limped off with a groin strain just before the interval.
Paul Lambert's men rarely threatened to score in the second half as they seemed to have run out of puff, although Ruddy did save well from David Perkins on 55 minutes, with the same player being thwarted by a block from impressive defender Dennis Lawrence shortly afterwards.
Colchester are now six points adrift of the top six, although boss Paul Lambert has not given up hope of his team mounting a late dash for the play-offs.