Michael O'Halloran's second goal for the Club wasn't enough for Rovers as they were defeated 2-1 at Leyton Orient.
After Orient had scored either side of half time and had a penalty saved by Owain Fon Williams, substitute O'Halloran pulled a goal back to give Ronnie Moore's side hope of stealing a point.
However, they were unable to find the all important second goal and left London empty handed.
There was just one change to the team that started against Carlisle with Cole Stockton replacing the suspended Jean-Louis Akpa Akpro in attack.
Charlie MacDonald had a chance to open the scoring in the third minute after running on to David Mooney's flick on but Donervorn Daniels did well to get a foot in and clear the danger.
The hosts dominated the early stages and after Lloyd James flashed a header wide of goal from six yards, Ash Taylor had to recover his own mistake, tracking back well to block Mooney's 18 yard effort after he had given the ball away in the middle of the Tranmere half.
Orient's early pressure paid off on eight minutes. A free kick conceded by Danny Holmes was curled towards the near post by Lee Cox and though MacDonald's first header was kept out by Owain Fon Williams, the striker reacted quickly to nod in from close range.
The home side could have been two up on 15 minutes. Dean Cox got past Taylor on the overlap and the Rovers defender caught the winger's legs after he got inside the area, with referee Trevor Kettle pointing straight to the penalty spot. However, Fon Williams guessed the right way to push Martin Rowlands' spot kick over the bar and Rovers dealt with the resulting corner.
A 30 yard free kick from Andy Robinson hit the Orient wall on 34 minutes while Daniels did well to head a cross away from MacDonald at the back post eight minutes later at the other end.
Orient pushed forward late in the first half. First Moses Odubajo raced forward on the overlap on 45 minutes and received the ball from Cox, cut inside and shot straight at Fon Williams, while Rowlands tried to catch the Rovers keeper off his line in injury time only for the Welshman to race back and catch his long range effort.
Mooney tried a right foot volley from 30 yards 12 seconds into the second half but his effort went wide of the target, while Lloyd James tried to capitalise on a loose ball a couple of minutes later but his attempt also failed to trouble Fon Williams.
Robinson sent a 12 yard shot over the bar on 54 minutes after Max Power dummied McGurk's corner while Rovers forced the home side back into their own half with a succession of set pieces around their box and shots from Amoo and Stockton.
However, Orient responded by doublingtheir lead. A free kick was cleared as far as Rowlands just outside the area and the midfielder unleashed a fantastic strike into the right side of Fon Williams' goal.
A double change from Ronnie Moore saw McGurk and Amoo replaced by Michael O'Halloran and Abdulai Bell-Baggie and the former reduced the deficit on 74 minutes. Power's through ball released Holmes into the right side of the area and his low cross through the six yard box was powered into the roof of the net at the back post by the Bolton Wanderers loanee.
Palmer twice tried to bring Rovers level, first seeing his shot blocked and then another effort from outside the area saved by Jones.
At the other end an underhit back pass from Taylor gave MacDonald a chance to kill the game off on 81 minutes but his attempt at curling past Fon Williams went out for a throw in.
Two minutes later the home side did get the ball in the Rovers net for a third time but Mathieu Baudry's header from a free kick was ruled out for offside.
Danny Holmes went close to an equaliser deep in injury time but his long range right foot shot was well saved by Jones.
Leyton Orient: Jones, Sawyer, Cuthbert, Baudry, Cox, MacDonald, Odubajo, Cook (Batt 78), Rowlands (Vincelot 84), James (Smith 66), Mooney. Substitutes: McSweeney, Griffith, Clarke, Grainger.
Tranmere: Fon Williams, Holmes, Taylor, Daniels, Bakayogo, McGurk (O'Halloran 70), Palmer, Power, Robinson, Stockton, Amoo (Bell-Baggie 70). Substitutes: Mooney, Kay, Goodison, Black, Harrison.
Referee: Trevor Kettle