Tranmere's final away fixture of the season ended in a high scoring defeat at the Weston Homes Community Stadium.
Goals early in the first and second halves put Colchester 2-0 up only for James Wallace to pull a goal back.
A goal credited as an own goal for Ian Goodison restored Colchester's advantage but Jake Cassidy again brought Ronnie Moore's side back into the contest.
However, their hopes of rescuing a point were ended six minutes from time when Colchester substitute Freddie Sears scored the home side's fourth of the afternoon.
There were three changes to the team that started against Hartlepool. The suspended Owain Fon Williams was replaced by Andy Coughlin, Mark McChrystal came in for Ash Taylor and Mustafa Tiryaki replaced Adam McGurk. An attacking looking bench for Rovers featured three strikers but no goalkeeper.
Rovers conceded from the first attack of the game. Colchester attacked down the right wing, the ball was sent into the penalty area from where Ian Henderson's header gave Coughlin no chance of a save.
It was almost two a couple of minutes later, with Coughlin saving well from Anthony Wordsworth, reacting well to keep another effort out from Lloyd James before Tranmere eventually cleared the danger.
Henderson's attempt at lobbing Coughlin saw the Colchester striker hit the top of the cross bar on 13 minutes, while Ian Goodison and Kayode Odejayi were both shown yellow cards for a scuffle four minutes later.
Rovers gradually worked their way into the match and began to have a greater share of the possession. Robinson completely missed his shot on 19 minutes while good work from Lucas Akins couldn't create an opening eight minutes later.
Tranmere's first shot came on 33 minutes when John Welsh brought a save out of Ben Williams after receiving the ball from James Wallace, and the midfielder was involved moments again, winning a corner after running on to a lofted pass from Akins.
Jake Cassidy had a chance to level when receiving the ball from Wallace inside the Colchester area on 39 minutes but the Wolves loanee was denied a shot on goal by the quick feet of Brian Wilson.
An early Henderson shot was blocked by Goodison moments after the second half started but from the resulting corner, the home side added their second when Tom Eastman rose highest to head past Coughlin.
Just when it looked like the game might be beyond them, Rovers pulled a goal back to reduce the deficit to one. Wallace received the ball 30 yards out and drove a low shot past Williams into the corner of the net for his second goal for the Club.
A low cross from Bakayogo wasn't capitalised on by his team mates while a Cassidy shot on the turn was comfortably saved by Williams.
Coughlin saved well from Bond on 64 minutes at his near post but the home side added their third from the corner, with Michael Rose's cross headed into his own net by Goodison under pressure from Okuonghae.
James fired over the bar on 66 minutes, while a Cassidy shot was well kept out by Williams a few minutes later at the other end.
A long range effort from Tiryaki was palmed behind for a Tranmere corner on 72 minutes and it brought Rovers' second goal. From Robinson's cross Akins fired in a shot which may have taken a touch off Cassidy and into the net to again reduce Colchester's advantage.
Martin Devaney and Adam McGurk were introduced in a double substitution which saw Akins and Robinson leave the action with 11 minutes remaining.
However, on 84 minutes Colchester added a fourth. While Wallace was down injured, the U's took advantage of their extra man, scoring through substitute Freddie Sears who cut in from the left and found the near corner of the goal.
Henderson almost added a fifth only for his shot to hit the post and rebound away from goal on 90 minutes, while Goodison fired against the keeper deep in injury time with Welsh heading over from the resulting corner.
Colchester: Williams, Wilson, Okuonghae, Eastman, White, Bond (Hamilton 87), James, Wordsworth, Rose, Odejayi (Gillespie 54 (Sears 79)), Henderson. Unused substitutes: O'Toole, Duguid.
Tranmere: Coughlin, Holmes, McChrystal, Goodison, Bakayogo, Akins (Devaney 78), Welsh, Wallace (Weir 87), Robinson (McGurk 79), Cassidy, Tiryaki. Unused substitutes: Brunt, Showunmi.
Referee: Andy Haines
Yellow cards: Odejayi (17), Goodison (17), Eastman (49), Tiryaki (60)
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