Paul Hayes netted a penalty and Fred Onyedinma found the net yet again either side of Jordan Hugill's equaliser, but they had to do it the hard way when Matt McClure was sent off just moments after coming off the bench.
It's the Blues' tenth league away win of the season and keeps confidence sky-high ahead of an important clash at Southend on Saturday.
Gareth Ainsworth kept faith with the same side that drew 2-2 with Stevenage at the weekend, which meant on-loan Brentford pair Sam Saunders and Nico Yennaris retained their places in a 4-4-2 set-up.
The visitors began brightly and caused panic inside eight seconds when Paul Hayes collected a long ball from kick-off and shot wide of the near post, before Sam Saunders blasted over the bar with his left foot after Danny Holmes could only clear Joe Jacobson’s cross into his path.
Wycombe were certainly settling the better of the two sides, forcing their relegation-threatened opponents into mistakes at the back, and one such error from Adam Dugdale resulted in him earning a yellow card for fouling Fred Onyedinma just outside the area, but Saunders’ free-kick was a yard too high.
Ainsworth’s men were well on top and it seemed just a matter of time until they would break the deadlock. The breakthrough came from the penalty spot on 26 minutes when Matt Bloomfield forced a handball inside the area and Paul Hayes confidently dispatched the penalty for his 10th goal of the season, even though keeper Owain Fon Williams dived the right way.
Tranmere responded well and Matt Ingram was called upon to keep out Marc Laird’s header from a deep cross, before the Rovers midfielder connected well with a cross but saw his shot deflected wide by Danny Rowe.
And if anything, Wycombe’s goal only served to wake Tranmere from their slumber and they deserved their leveller on 31 minutes when a dangerous cross into the box was met by Jordan Hugill, who forced it over the line.
Rovers were suddenly in the ascendancy so it came as a surprise to most when Wycombe regained the lead on 40 minutes, and it came from nothing as Sido Jombati clipped a ball over the top to find Fred Onyedinma who had escaped his man. The on-loan Millwall man kept his composure to slot the ball past Fon Williams for his fifth goal in four games, and his eighth goal in 12 starts in total for the men in light and dark blue.
The half-time advantage came with the caveat that the visitors would need to work hard to thwart Tranmere’s threat from crosses, particularly with Lee Molyneux’s ability with the ball at his feet, and Kayode Odejayi’s aerial presence.
A deep free-kick early in the second half fell for Marc Laird whose goalbound volley was blocked to safety, before Wanderers were denied what looked a certain penalty at the other end when Sam Wood did superbly to beat his man and play a one-two with Hayes before being felled just before he was set to pull the trigger.
Then Jordan Hugill was sent clear down the left but blasted high and wide as Danny Rowe closed in, before Micky Adams attempted to lift his side with a double substitution on the hour-mark, bringing debutant Dan Gardner and veteran Iain Hume into the fray.
Joe Jacobson fired a dangerous free-kick just over the bar and Sam Saunders shot straight at the keeper after cutting in from the left as the Wanderers looked to extend their lead, before at the other end, Alfie Mawson led by example with three superb pieces of defending in quick succession to thwart some dangerous Rovers crosses.
But then the defence knew they had a battle on their hands when Wycombe were reduced to 10 men as Matt McClure was shown a red card just seconds after replacing Sam Saunders from the subs’ bench, with the referee adjudging his aerial challenge with Adam Dugdale to have been an intentional arm to the face.
To Wanderers’ credit, they didn’t play like a team with a one-man deficit, and almost stretched their lead when Joe Jacobson burst through an inviting hole in the defence and forced Fon Williams into a smart save, before his opposite number Matt Ingram stuck out a strong arm to deny Max Power at the other end with eight minutes remaining.
The tension grew when Sam Wood was called into action to clear off his own goal-line when Michael Ihiekwe met a corner with a bullet header, but whatever Rovers had to throw at them, Wycombe had an answer and held on for a memorable victory.
Wycombe: Ingram, Jombati, Jacobson, Mawson, Rowe, Saunders (McClure 67), Yennaris, Bloomfield (Murphy 89), Wood, Hayes, Onyedinma (Craig 89).
Unused subs: Richardson, Fletcher, Ephraim, Holloway.
Tranmere: Fon Williams, Holmes, Ihiekwe, Dugdale, McGahey (Gardner 60), Laird, Power, Jennings (Kirby 72), Molyneux, Hugill (Hume 60), Odejayi.
Unused subs: Ramsbottom, Ridehalgh, Koumas, Thompson.
Referee: Mr M Heywood