Reus picked up an ankle injury against Schalke 04 in September and has not played for Borussia Dortmund since.
Reus has also suffered untimely injuries in the past on the cusp of major tournaments, missing Germany's victorious 2014 FIFA World Cup campaign and EURO 2016 with last-minute setbacks.
Reus also opted out of last summer's European championship to recover from a gruelling season for Dortmund after making 48 appearances across all competitions in the 2020/2021 campaign.
There is however a surprise recall after five years for 2014 World Cup hero Mario Gotze and Borussia Dortmund's 17-year-old Youssoufa Moukoko has been included as well.
There is no place for the experienced Matts Hummels and injured RB Leipzig star Timo Werner had already been ruled out of the tournament.
Germany failed to qualify from their group as defending champions four years ago but will be looking to finish in the first two positions this time in a group that also featured Spain, Costa Rica and Japan.
Germany's World Cup squad in full:
Goalkeepers: Manuel Neuer (Bayern Munich), Marc-Andre ter Stegen (Barcelona), Kevin Trapp (Eintracht Frankfurt)
Defenders: Matthias Ginter (Freiburg), Antonio Rudiger (Real Madrid), Niklas Sule (Borussia Dortmund), Nico Schlotterbeck (Borussia Dortmund), Thilo Kehrer (West Ham United), David Raum (RB Leipzig), Lukas Klostermann (RB Leipzig), Armel Bella-Kotchap (Southampton), Christian Gunter (Freiburg)
Midfielders: Ilkay Gundogan (Manchester City), Jonas Hofmann (Borussia Moenchengladbach), Leon Goretzka, Serge Gnabry, Leroy Sane, Jamal Musiala, Joshua Kimmich, Thomas Muller (all Bayern Munich), Julian Brandt (Borussia Dortmund), Mario Gotze (Eintracht Frankfurt)
Strikers: Kai Havertz (Chelsea), Youssoufa Moukoko (Borussia Dortmund), Niklas Fullkrug (Werder Bremen), Karim Adeyemi (Borussia Dortmund)
