A second half winner by Jordan Moore-Taylor gave Exeter City all three points at Prenton Park. The Grecians took an early lead through Graham Cummins which Danny Holmes cancelled out for Tranmere before Moore-Taylor's decisive effort sealed the points for the visitors.
Tranmere made one change to the side which started against Newport County on Tuesday night. Ben Davies, on loan from Preston North End, made his debut in place of the injured Matt Hill at left-back. Matt Gill and Eliot Richards both started against their former club.
Exeter had the first opportunity on goal after 6 minutes and it ended with the ball in the back of the net. A ball forward found David Wheeler on the edge of the box. The winger tried to lob Owain fon Williams who his fingertips to the ball which spun into the air and striker Graham Cummins was on hand to head in from close range to give the Grecians the lead.
Tranmere came back and forced Exeter goalkeeper Christy Pym into a smart save on 9 minutes. Abdulai Baggie and Cole Stockton linked up to play in Eliot Richards who shrugged off a defender and fired a low shot which Pym saved well down to his right.
On 11 minutes, the Grecians had a chance to extend their advantage. A ball from the left evaded the Tranmere defence and Liam Sercombe came in on the blind side but his volley went into the side netting.
Exeter thought they had gone 2-0 up on 23 minutes. A shot from distance was deflected into the path of Cummins who rounded fon Williams and put the ball in the net, only for the assistant referee to indicate that he was in an offside position.
And a couple of minutes later, the scores were level. Stockton spread the ball wide to the right where Danny Holmes cut inside and drove a low left-footed shot from 20 yards which went into the bottom corner of the net via a slight deflection.
Rovers almost took the lead just before the half-hour mark. A ball into the box found Richards who controlled, turned and hit the rising ball but he couldn't direct his effort from eight yards on target.
There was another good chance for Tranmere on 34 minutes. Max Power did well to beat Craig Woodman to the ball on the right. He cut the ball back for Stockton whose effort slid across the face of the goal and wide of the target.
The same duo combined again a minute later. A high cross by Power found Stockton in the six yard box but the striker was at full stretch and could not direct his header on target.
On the stroke of half-time, a deep cross from the left by Exeter's Matt Grimes found Wheeler at the back post but his header drifted wide of the goal as the sides went in level at the interval.
Five minutes into the second half, Power curled an effort from 25 yards straight at Pym while at the other end, Janoi Donacien blocked a shot from Arron Davies which skidded just wide of the goal.
Exeter had the ball in the net again on 53 minutes but again the goal was ruled out for offside. A cross from the right by Davies was bundled in by Cummins whose joy was short lived with the sight of the assistant referee's flag.
On 56 minutes, the Grecians hit the post. A cross from the left found Wheeler who side-footed a shot onto the outside of the post, although the assistant had again flagged for offside.
Tranmere made a double substitution on 58 minutes with George Donnelly and Kayode Odejayi coming on to replace Stockton and Richards.
The third and final Rovers change came just after the hour-mark and saw Jason Koumas come on to replace Matt Gill in midfield.
Odejayi has his first sight of goal on 66 minutes. Holmes put in a low cross from the right which the former Nigerian international blasted just wide.
A minute later, Koumas tried his luck from 25 yard but his left foot shot was dragged wide.
The visitors took the lead again on 69 minutes. A free-kick from the left was curled into the penalty area by Grimes and Jordan Moore-Taylor thumped a header past fon Williams and in off the crossbar.
On 76 minutes, Holmes and Baggie linked on the right with the latter playing in Marc Laird whose shot hit the side netting.
The ball was played straight down the other end and a cross from the right found Cummins at the back post but the Exeter striker's header was misplaced and went wide.
The next attack saw a chance for Tranmere. A cross into the box by Holmes was met by Odejayi but he couldn't control his finish and the ball drifted wide.
With six minutes remaining, Koumas hit a free kick from 25 yards which curled narrowly wide, while a minute later Odejayi mistimed a header and the opportunity was cleared by the Exeter defence as the Grecians held on to take all three points.
Tranmere: Fon Williams, Holmes, Donacien, Ihiekwe, Davies, Baggie, Power, Gill (Koumas 61), Laird, Richards (Odejayi 57), Stockton (Donnelly 57). Substitutes: Brezovan, Holness, Rowe, Fanimo.
Exeter: Pym, Woodman (Keohane 64), Ribeiro, Sercombe, Oakley, Davies, Grimes, Moore-Taylor, Wheeler (Butterfield 68), Nicholls, Cummins (Nichols 81). Substitutes: Noble, Dawson, Hamon, Tillson.
Referee: Mick Russell
Yellow cards: Gill (10), Laird (87)