It was fast and furious from the outset and three goals came in a golden seven-minute spell.
Tranmere could have been ahead in the fourth minute but Aaron Cresswell was denied a debut goal from a free-kick by a fine diving save from Adam Federici.
But Federici could do nothing about an Ian Moore volley just inside the box from Chris Shuker's cross in the eighth minute.
United responded immediately with Alex Revell somehow flicking a Kevin Betsy cross over keeper Danny Coyne two minutes later.
Tranmere kept roaring forward and Bas Savage was allowed to make ground before beating Federici with an excellent strike from 20 yards.
The Merseysiders should have added to their lead but Moore and Savage missed the target from clear openings and Federici made good saves from Steve Jennings and Antony Kay.
Southend weathered the storm and levelled totally against the run of play in the 35th minute when Betsy fired home after a Hal Robson-Kanu shot had rebounded off a post.
Chris Greenacre fired into the side-netting for Tranmere soon after the break while at the other end Coyne blocked a Robson-Kanu effort.
Tranmere were almost ahead again in the 62nd minute but Kay struck the outside of a post from Shuker's cross.
Kay was always in the thick of the action for Tranmere who looked dangerous every time they moved forward.
Southend had many anxious moments in defence but stuck to their task admirably well led by skipper Adam Barrett.
They had Francis Laurent dismissed in the 71st minute for a head-butt on Ryan Shotton during a flare-up. Tranmere were also reduced to ten men 12 minutes later when Steve Jennings picked up a second yellow card.