Michail Antonio scored to give the hosts a half-time lead before Nile Ranger added a second early in the second half to clinch second spot, three points ahead of Sheffield United who could only draw at Exeter.
After Wednesday pair Mark Beevers and Jose Semedo had both put efforts off target, Nikki Bull came to Wycombe's rescue with a superb reflex save to keep out Miguel Llera's effort.
Bull also tipped over a Llera header before Antonio opened the scoring in the 25th minute after bursting into the area and slotting the ball past the Wycombe goalkeeper.
Ranger gave the home side the cushion they craved in the 52nd minute when he made it two-nil, rising unchallenged in the area to meet Chris Lines' free-kick with a header. And the Newcastle loanee threatened to add a third but his goalbound shot from close range was blocked.
Wycombe failed to even test Stephen Bywater in the Wednesday goal, the nearest they came to scoring coming when Matt Bloomfield's long-range effort flashed narrowly wide. Llera was then denied a late goal when Bull pulled off a superb save from his header.