Freddie Sears and Armando Dobra struck in the first half as the U's pick up another three points at the JobServe Community Stadium.
Freddie Sears got the U's off to a flying start within five minutes when he lofted the ball over Watson and into the far corner, with Armando Dobra's curling effort doubling the advantage for the home side ten minutes later.
Harry Davis got one back for the visitors ten minutes before the end of the game, but the U's were able to hold on and claim three points at the JobServe Community Stadium.
Hayden Mullins named a line up with four changes to the starting eleven that lost against Sutton United on Tuesday evening.
Coming in to the line up was Wiredu, Jasper, Eastman and Dobra, with Smith, Hannant, Kennedy dropped to the bench and Samson Tovide missing through suspension.
New signing, Shawn McCoulsky was named as a substitute after putting pen-to-paper on a short term deal with the U's earlier on Saturday.
Once again at the JobServe Community Stadium, the U's made a fast start, taking the lead within the five minutes. It was Freddie Sears who gave the U's the advantage early on again, when he flicked the ball from Charlie Daniels cross over Watson's head and into the far corner.
And as there was on Tuesday night against Sutton United, there was another goal in the fifteenth minute. But this time it was the U's doubling their advantage through an outstanding Armando Dobra strike.
Cutting in from the left wing, Dobra got the better of Ross Millen and lofted the ball over Watson's head and into the back of the net, making it 2-0 to the U's with quarter of an hour gone.
Colchester United were inches away from making it 3-0, when Sylvester Jasper's marauding ended with a fierce strike that crashed against the cross bar and away from danger.
Noah Chilvers had a shot that tested the reflexes of Rory Watson in the final chance of the half for the U's, but Hayden Mullins' side headed to the changing rooms at half time with a comfortable advantage over Scunthorpe United.
After the break, the U's had to weather the storm from Scunthorpe, as the visitors went in search of a route back into the game.
But a couple of simple saves for George ensured the U's kept their two-goal advantage before the U's were able to get back in their attacking stride and put pressure on the Irons' defence again.
With sixty minutes played, Freddie Sears went close to getting his second, and the U's third after some good work in the middle of the field from Cole Skuse.
The combative midfielder won the ball back, playing it through to Sears who took his time to settle on the ball before crashing an attempt against the bar. Dobra won a corner from the follow up but the U's were back at the right end of the pitch, looking for a third.
The U's took their foot off the gas a little though with fifteen minutes to go, and Scunthorpe sensed they might be able to find a way back into the game.
Neil Cox's side did find a lifeline with ten minutes to play, when Harry Davis capitalised on the U's failure to clear the ball from the back. The ball was headed against the bar, with Davis tapping into the unguarded net.
Colchester United were able to hold on in the final ten minutes though and claim a second three points in four home games.
The U's move up to seventeenth in Sky Bet League Two with seventeen points from fifteen games going into the FA Cup
Colchester United starting XI: George, Welch-Hayes, Chambers, Wiredu, Skuse, Sears (Clampin 87'), Chilvers, Jasper (Nouble 64'), Eastman, Dobra (Hannant 90'), Daniels.
Unused Subs: Turner, Smith, McCoulsky, Kennedy.
Scunthorpe United starting XI: Watson, Millen, Taft, Onariase, Loft (Jarvis 61'), Hippolyte (Green 46'), Thompson, Scrimshaw, Pugh (Beestin 46'), Davis, Hackney.
Unused Subs: Balme, Rowe, Wood, Jarvis, O'Neill.