The Reds struggled to make in-roads against the League Two side in the opening 45 minutes but, once Marcus Rashford struck the opener, the result was never in any doubt.
An own goal by Ryan Jackson quickly doubled the advantage, and Anthony Martial got in on the act from close range to cap an entertaining spell of football.
As expected the match was played mainly in Colchester’s half with Reds goalkeeper Sergio Romero probably able to ponder on what Christmas presents he had yet to buy.
In earlier rounds, the Essex side knocked out Premier League opposition in Crystal Palace and Spurs on penalties, without scoring in normal time, and it looked like they’d hope to survive for a similar outcome at Old Trafford.