Like the home side, Rotherham earned promotion from League One last season, finishing in second place behind champions Coventry City.
Just over 13 months on from being tipped as one of the favourites to get relegated to League Two, Wycombe are beginning life in the Championship, heading into the unknown with nothing but excitement.
Provided with minimal transfer funds during his time at Adams Park, Gareth Ainsworth has worked miracles to get the club to this point, but Wycombe's long-serving boss is driven to pull off an unlikely survival story.
In order to compete at this level, the club's hierarchy have provided Ainsworth with a budget which has enabled him to bring in some noteworthy fresh faces, a list which includes Hibernian winger Daryl Horgan and ex-Birmingham City goalkeeper David Stockdale.
Both players will require time to settle into life in a band-of-brothers-style environment behind the scenes, but their presence will likely be necessary if their new club is going to stay at this level of the English football pyramid.
Wycombe showed against Brentford in the EFL Cup that they are capable of raising their game to the required level, although consistency is everything when looking to establish yourselves in a division as competitive as the Championship.
That is something which is not lost on opponents Rotherham, who have spent the last four years being promoted and relegated between the second tier and League One.
In their two most recent efforts in the Championship, the Millers have recorded just 13 wins from 92 matches, highlighting the level of difficultly facing Wycombe.
Nevertheless, Rotherham have evolved since Paul Warne's arrival in 2016, and there is a feeling that they have not being better equipped to survive in this division for some time.
While the arrival of Chelsea goalkeeper Jamal Blackman stands out, the signings of defensive duo Angus MacDonald and Wes Harding from Hull City and Birmingham City respectively could prove to be the difference when it comes to avoiding a third successive relegation when taking part at this level.
Wycombe Wanderers form (all competitions): D
Rotherham United form (all competitions): D
Neither manager is expected to make many alternations to their respective lineups for this fixture.
Matt Crooks could be handed a start by Rotherham boss Warne after his appearance as a substitute against Salford City.
As it stands, Trevor Clarke's calf injury is the only fitness issue ahead of this contest.
Despite the recent addition of Stockdale, Ryan Allsop will keep his spot between the sticks for Wycombe.
Wycombe Wanderers possible starting lineup:
Allsop; Grimmer, Stewart, Charles, Jacobson; Horgan, Thompson, Bloomfield, Onyedinma; Samuel, Parker
Rotherham United possible starting lineup:
Blackman; Harding, MacDonald, Ihiekwe, Mattock; Ogbene, Crooks, Lindsay, Sadlier; Ladapo, Smith
We say: Wycombe Wanderers 1-1 Rotherham United
While both clubs will view this game as an opportunity to get off to the perfect start, we are expecting a tense affair at Adams Park. Despite the enthusiasm within both ranks, do not expect many goals in this one. If there are any, they could be shared out.