A first half strike from Alfie Beestin sealed all three points for the visitors as Scunthorpe consign the U's to just a second home defeat of the season.
The game was settled in the fifth minute by a strike from Beestin that hit the top corner, with Neil Cox's side heading back to Scunthorpe with all three points.
Chances from the U's went begging, in the second half, as the tried to get themselves back on level terms, with Steve Ball's side dropping to sixteenth place.
Steve Ball named an unchanged side for his starting eleven to face Scunthorpe United.
It was the same eleven that came away from Stevenage with a point after a goalless draw in the week, although there were changes to the bench. Tom Lapslie and Ryan Clampin came onto the substitutes bench, with Harvey Sayer and Junior Tchamadeu missing out on the matchday eighteen.
There was no time to settle into the game under the lights at the JobServe Community Satdium, with the visitors taking the lead in under five minutes.
Alfie Beestin ran unchallenged before unleashing an unstoppable shot that flew into the top corner, leaving Gerken rooted to the spot as the Iron took an early goal advantage.
With just a quarter of an hour played, there was a string of early changes: two for Colchester United and once for Scunthorpe United.
Ben Stevenson and Dean Gerken were forced off with injuries, being replaced by Tom Lapslie and Shamal George, with the sub 'keeper making his league debut for the U's, while Karacan was replaced by Spence after a heavy challenge from Harriott.
Following the substitutions, there was a settling in period, with both sides unable to keep the ball for long spells as the new players got into the game.
Colchester United seemed to adapt to the changes quicker, pushing forwards to try and fnid the equaliser, although the visitors looked dangerous on the break with former U's loanee Abo Eisa and Ryan Loft leading the attacks.
Loft's driven cross looked as though Green may get to the ball at the back post, but George put the ball behind to prevent the Scunthorpe man from getting his to toe the cross.
The injuried weren't limited to the players in the first half, when with five minutes to play, the nearside linesman was forced to take the job of the fourth official, while the man separating the two dugouts took the flag on the nearside.
With all the stoppages there was an additional seven minuted that was played at the end of the first half before the two sides headed for the changing rooms.
The U's needed a goal, and came racing out looking for the equaliser. Courtney Senior's driving run looked as though he would go all the way, but for being halted by a good challenge from Onariase as they entered the penalty area. The Scunthorpe man had to put in a good challenge and did so, picking the ball off Senior's toe.
U's Head Coach Steve Ball made the call to swap the wingers, with Harriott coming over to the right and Senior heading over to the left, and it almost had an instant impact for his team.
Callum Harriott tried his luck with a dipping effort from just outside the area, with Howard spilling the ball, although there was no one following up to attack the ball before the visiting 'keeper collected at the second attempt.
Harriott's attempt two minutes later came from almost the same position although it ended differently. He cut in and powered a left foot effort towards the top corner, but with the ball always rising, Howard happily saw it lift over the bar.
Scunthorpe once again were dangerous on the counter attack, with Loft and Eisa combining well.
Twice the visitors had the ball in the net, before the goal was ruled out for offside, as the U's pressed further and further forwards to try and get themselves back on level terms.
Cohen Bramall tried to sneak in an equaliser with a free kick from a tight angle, but Junior Brown cleverly blocked the ball at a low height with the near post open.
The U's were unable to find an equaliser and were consigned to just a second home league defeat of the season.
Colchester United starting XI: Gerken (George 16'), Welch-Hayes, Bramall, Smith, Senior, Brown (Folivi 78'), Harriott, Chilvers, Eastman, Poku (Oteh 60'), Stevenson (Lapslie 15').
Unused Subs: Sowunmi, Clampin, Marshall Miranda.
Scunthorpe United starting XI: Howard, Taft, Onariase, Gilliead, Loft (Hippolyte 82'), Eisa, Brown, Green (McAtee 69'), Beestin, Karacan (Spence 17'), Rowe.
Unused Subs: Watson, Bedeau, Hallam, O'Malley.