The two neighbouring cities have a friendly rivalry off the pitch, and on the pitch the two sides have only met on five previous occasions this century.
Match preview
Wiesbaden were relegated from 2. Bundesliga last season after losing their relegation play-off to Jahn Regensburg in May, but Nils Doring's side have made a solid start to their league campaign.
The hosts come into this game on the back of a 1-0 home victory over FC Hansa Rostock, where a solitary goal from Moritz Flotho was enough to secure all three points.
Die Rot-Schwarzen are now unbeaten in their opening two league games, having drawn their first game of the season 2-2 away at SC Verl.
New signing Flotho now has two goals in two games, and his clinical half-volley finish against Hansa Rostock demonstrated his finishing ability when provided with an opportunity in front of goal.
Wiesbaden have been busy in the summer transfer window so far, bringing in 12 players as they look to reclaim their spot in the second tier of German football come the end of the campaign.
This is also the second consecutive season that Wiesbaden have faced a Bundesliga side in the first round of the DFB-Pokal, having been eliminated by RB Leipzig last season in a plucky 3-2 home defeat.
For Mainz, this will be their first competitive game of the season having rounded off their pre-season fixtures with a 3-1 home victory over Montpellier on Saturday.
Goals from Andreas Hanche-Olsen, Phillipp Mwene and Nelson Weiper were enough to see the 05ers end what has been a goal-laden pre-season that has seen Bo Henriksen's side score a remarkable 15 goals in just four games.
This is Henriksen's first full season for Mainz having joined from FC Zurich in February, and his side come into this season on an unbeaten league run of nine games.
Following a bruising 8-1 defeat at the hands of Bayern Munich in March, Mainz's upturn in form saw them record impressive wins over the likes of Hoffenheim, Borussia Dortmund and Wolfsburg towards the end of the season.
If Mainz are to continue their fine form into this season a lot will depend on the attacking output of Jonathan Burkardt and Jae-sung Lee, with the pair scoring 14 goals between them last season.
Wehen Wiesbaden form (all competitions):
Mainz 05 pre-season form:
Team News
Faith Kaya (ankle) will be missing for Wiesbaden, and left-back Nico Rieble (muscle) will also be absent for the cup clash on Friday.
Doring will have to choose who supports Flotho in attack, with Ivan Franjic and Tarik Gozusirin being the most likely candidates to start.
For Mainz, new signing Kaishu Sano could make his first official start for the club, with Bayern Munich loanee Armando Sieb also pushing for a starting berth.
Maxim Leitsch (adductor) is the only long-term absentee, having been out since the middle of February with his injury.
In midfield, the likes of Nadiem Amiri, Paul Nebel and Brajan Gruda will be pushing for starts here.
Wehen Wiesbaden possible starting lineup:
Stritzel; Mockenhaupt, Carstens, Luckeneder; Goppel, Fechner, Batzner, Greilinger; Franjic, Gozusirin; Flotho
Mainz 05 possible starting lineup:
Zentner; Hanche-Olsen, Fernandes, Caci; Gruda, Kohr, Sano, Mwene; Amiri, Lee; Burkardt