The better chances early on fell to the visitors but Luke Daniels made a fine save from a David Fox free kick and Kayode Odejayi just missed the target after a defensive error.
Michael Ricketts and Ian Thomas-Moore tested United keeper Ben Williams before Tranmere edged in front in the 35th minutes when Williams did well to block a powerful Marlon Broomes strike but John Welsh netted from the rebound.
The lead lasted just two minutes with John-Joe O'Toole equalising for United from an Odejayi cross and Magnus Okuonghae wasting a simple headed chance to put Colchester in front.
Both went close in the second half, Tranmere via Chris Shuker and Colchester through Clive Platt and Magnus Okuonghae.
Tranmere thought they had won it in the 89th minute but a Kitson Bain strike was ruled out by the referee's assistant for offside.