Jabo Ibehre's double pulled Colchester out of the relegation zone and heaped more misery on Stevenage.
George Porter's effort was cleared off the Boro goaline, before Anthony Grant drew a fine save from Sam Walker at the other end.
But Ibehre struck twice in the second half, heading in Billy Clifford's free-kick and tapping in a simple chance.
Gary Smith's Stevenage have now lost six in succession and have taken six points from the last 39 available.
They are seven points clear of League One's bottom four though, while the U's have created a two-point safety cushion.
VIEW FROM THE DRESSING ROOM
Stevenage manager Gary Smith told BBC Three Counties Radio:
"It's the toughest challenge without a shadow of a doubt that I've faced as a young manager.
"The players are very good individuals, they're very good characters - they're feeling the pinch at the minute, we all are.
"Our challenge is probably three wins to make sure we secure our League One status and I have absolutely no doubt in the last 12 games we can get that.
"The chairman's a very good guy, he's a good businessman - it's his prerogative to make changes, but I'd be deeply disappointed at this stage."
Colchester United manager Joe Dunne told BBC Essex:
"The result speaks for itself, it was never easy.
"For the first time in a while, we really got the ball down and played. We had a game plan and I thought we could find a bit of confidence with the ball. We did that, which was great.
"We said at half-time if we can create the same amount of chances, we would finish them. All we needed was the finishing touches on our moves and we got them.
"The effort and the commitment has given us the reward."