The 20-year-old has made an impressive start to life on the South coast following his summer switch from Bundesliga club VfL Bochum.
Bella-Kotchap, who has started in each of Southampton's last five Premier League fixtures, has featured nine times for Germany's Under-21s, with his most recent appearance against Poland in June.
However, the young defender will now get the chance to test himself with the senior team as he is one of 24 players who has been selected in Flick's squad ahead of their final two fixtures before the World Cup begins in November.
Barcelona goalkeeper Marc-Andre ter Stegen, Borussia Monchengladbach centre-back Matthias Ginter and Inter Milan left-back Robin Gosens have also been included after missing the last international break in June.
Hoffenheim stopper Oliver Baumann, RB Leipzig defenders Benjamin Henrichs and Lukas Klostermann, and Bayer Leverkusen centre-back Jonathan Tah have all been dropped from the squad, while Borussia Dortmund's Mats Hummels has been left out once again.
Bella-Kotchap is one of four Premier League players in the Germany squad along with Manchester City's Ilkay Gundogan, Chelsea's Kai Havertz and West Ham United's Thilo Kehrer.
Borussia Dortmund's Marco Reus could make his 49th and 50th appearances for Die Mannschaft should he play in both international fixtures this month, while Bayern Munich duo Manuel Neuer and Thomas Muller - who have 229 caps combined - are the most experienced members of Flick's squad.
Germany are scheduled to face League A Group 3 leaders Hungary in their penultimate Nations League match at the Red Bull Arena on September 23, before locking horns with Euro 2020 finalists England at Wembley Stadium in their final match three days later.
Germany's 24-man squad in full:
Goalkeepers: Manuel Neuer (Bayern Munich), Marc-Andre ter Stegen (Barcelona), Kevin Trapp (Eintracht Frankfurt)
Defenders: Armel Bella-Kotchap (Southampton), Matthias Ginter (Freiburg), Robin Gosens (Inter Milan), Thilo Kehrer (West Ham United), David Raum (RB Leipzig), Antonio Rudiger (Real Madrid), Nico Schlotterbeck, (Borussia Dortmund), Niklas Sule (Borussia Dortmund)
Midfielders/Attackers: Julian Brandt (Borussia Dortmund), Joshua Kimmich (Bayern Munich), Leon Goretzka (Bayern Munich), Ilkay Gundogan (Manchester City), Jamal Musiala (Bayern Munich), Jonas Hofmann (Borussia Monchengladbach), Thomas Muller (Bayern Munich), Marco Reus (Borussia Dortmund), Serge Gnabry (Bayern Munich), Leroy Sane (Bayern Munich), Lukas Nmecha (Wolfsburg), Timo Werner (RB Leipzig), Kai Havertz (Chelsea)