Top of the table Charlton Athletic took all three points from their League One trip to Prenton Park.
It was an afternoon to forget for Rovers as two goals in a minute in the first half put the Addicks in charge of the contest and a third early in the second half ended hopes of a come back. A bizarre fourth completed the defeat with more than 20 minutes remaining.
There were three changes to the side that started the Carling Cup tie against Bolton Wanderers, with Gavin Gunning, Shaleum Logan and Ian Thomas-Moore coming back into the starting XI in place of Ash Taylor,Gareth Edds and Craig Curran.
Charlton started the game brightly and spent the first couple of minutes camped in the Tranmere half. However, some strong play from Ian Thomas-Moore allowed Rovers to start their first attack on four minutes and the move ended up with Charlton full back Kelly Youga being shown a yellow card for a foul on Chris Shuker.
Rovers keeper Luke Daniels saved well from Jonjo Shelvey on eight minutes after referee Paul Tierney waved play on following a foul from Aaron Cresswell.
A cross from Alan Mahon gave Charlton keeper Rob Elliott a problem on 12 minutes, while at the other end Daniels palmed Deon Burton's 18 yard shot over the bar.
The visitors took the lead on 24 minutes. Charlton cleared quickly from a Rovers free kick deep, broke down the left from where Shelvey sent in a cross. Lloyd Sam got in front of Cresswell and sent his header into the left side of the net from eight yards.
A minute later it was 2-0 to Charlton. Burton's neat back heel sent Jose Semedo through on goal and the midfielder turned the ball past Daniels into the bottom left corner.
Nicky Bailey's long range effort was two yards wide on 32 minutes, while Paul McLaren fired a free kick straight at Elliott from 25 yards six minutes later as Rovers looked for a way back into the game.
Rovers' best chance of the half came on 44 minutes. McLaren played the ball wide to Cresswell and his cross was turned goalwards by Thomas-Moore, though Elliott comfortably saved.
The start of the second half brought two changes for Rovers. On came Gareth Edds and Michael Ricketts, with Mahon and Shuker leaving the action. The moves also saw a change of formation with Rovers now playing 4-3-3.
On 48 minutes Welsh volleyed narrowly wide from a Ricketts cross as the home side showed early signs of improvement.
However, a minute later Charlton scored their third, this time Sam heading in at the far post from a left wing cross.
The Addics continued to attack, with Bailey shooting wide from distance and Shelvey heading just past the post
Rovers' third change saw Gornell replaced by Ryan Fraughan, but the winger had only been on the pitch a minute when Charlton made it four. A cross from deep on the left from Bailey somehow went straight through the Rovers area and into the far post beyond Daniels' outstretched arm.
On 76 minutes Goodison was first to a Ricketts flick on from a free kick but his volley went over the bar from six yards out, while Edds shot at Elliott after good work from Fraughan four minutes later.
McLaren cleared from his own goal line on 84 minutes under pressure from Llera and the midfielder headed at Elliott at the other end six minutes later from an Edds cross.
Tranmere: Daniels, Logan, Goodison, Gunning, Cresswell, Shuker (Edds 45 HT), Welsh, McLaren, Mahon (Ricketts 45 HT), Gornell, Thomas-Moore. Substitutes not used: Collister, Taylor, Fraughan, Barnett, Curran.
Charlton: Elliott, Richardson, Youga, Bailey, Llera, Semedo (Spring 76), Shelvey (Tuna 83), Racon, Burton, Sam, Dailly. Substitutes not used: Randloph, McLeod, Solly, Wagstaff, Basey.
Referee: P Tierney
Yellow cards: Youga (4), Logan (15), Gornell (56), Llera (63)