Ainsworth, who has gained huge plaudits for his guiding of the Adams Park club to the Championship last season, is missing after undergoing back surgery yesterday.
The 47-year-old is the second longest-serving manager in the Football League behind Harrogate Town’s Simon Weaver having lead the club for over eight years.
His opposite number, Sheffield Wednesday boss Garry Monk, has made five changes to the side that lost at Rotherham in midweek, with Joe Wildsmith replacing Cameron Dawson in goal and Dominic Iorfa making his long-awaited return to fitness.
Liam Palmer, Adam Reach and Josh Windass also come into the starting line-up.
A pre-match tweet from the official Wycombe Wanderers account confirmed Ainsworth’s absence.
“Richard Dobson will take charge of the #Chairboys today,” it said, “with Gareth Ainsworth absent after undergoing surgery on his back yesterday.”