First-half goals from Steve Old and Adam McGurk made it three home wins in a week for the Shrimps.
Adebayo Akinfenwa pulled one back for the visitors as they dominated the second half but a man-of-the-match performance from Morecambe keeper Barry Roche earned victory.
Having made multiple changes for Tuesday’s Checkatrade Trophy tie against Leicester City, Jim Bentley’s line-up showed only one new face from the side which defeated Hartlepool United in the FA Cup.
Sam Lavelle was named alongside Old in the centre of defence, replacing Max Muller who was ineligible under the terms of his loan from Wycombe to the Shrimps.
Though the visitors had the first effort of the match with Roche palming out Nick Freeman’s effort, it was Morecambe who carried the greater attacking threat.
One swift counter-attack ended with Aaron Wildig shooting wide, while McGurk’s 35-yard chip drifted narrowly over the Wycombe bar with keeper Scott Brown beaten.
Andy Fleming also volleyed wide before Old opened the scoring on 27 minutes.
Wildig’s corner was cleared back out to the midfielder, whose cross was met by the onrushing Old with a header which gave Brown no chance.
Freeman dragged a shot wide of the home goal, while McGurk volleyed out of the ground from Garry Thompson’s chip.
He was not so charitable with half-time a minute away, finishing clinically with a low shot to Brown’s right-hand side.
There was still time before the break for Kevin Ellison to go close to a third goal for the home side but his effort was narrowly wide of goal.
If the first half was about Morecambe being on the front foot, the second period was more about their defensive work.
Thompson shot wide and Ellison had a free-kick blocked but much of the second period was about frustrating their visitors and limiting their attacking opportunities.
Sam Saunders, Marcus Bean and Akinfenwa all failed to test Roche, though the Shrimps’ keeper was soon to make two quickfire saves.
The first came to deny Akinfenwa after Anthony Stewart had advanced forward and played the ball into the striker, who turned and saw his low effort well saved.
Save number two kept out Saunders’ curled effort from distance, which proved the midfielder’s last involvement as Wycombe freshened up their line-up in a bid to rescue a point.
Roche kept out Freeman’s volley before Akinfenwa halved Wanderers’ deficit with a close-range finish on 82 minutes, setting up a nervy finish.
They were almost level seconds later as the striker headed inches wide before Craig Mackail-Smith curled off target and Roche held another Freeman attempt.
Akinfenwa then headed off target again in added time as Morecambe clung on for three points.
Morecambe: Roche, McGowan, Old, Lavelle, Brough, Kenyon, Fleming, Thompson, Wildig (Oliver 81), Ellison, McGurk (Rose 85). Subs not used: Nizic, Campbell, Lund, Osborne, Lang.
Wycombe Wanderers: Brown, Gape (Cowan-Hall 68), Stewart, Scarr, Jacobson, Eze (Bloomfield 79), Bean, Saunders (O’Nien 68), Mackail-Smith, Akinfenwa, Freeman. Subs not used: Ma-Kalambay, Jombati, El-Abd, Southwell.
Referee: Andy Haines.