The Arsenal forward has been in fine form for Mikel Arteta's side this term, scoring six goals in 10 appearances across all competitions, including four goals in seven Premier League matches.
Havertz was on the scoresheet and played the full 90 minutes in the Gunners' 3-1 comeback victory at home to Southampton on Saturday, equalling a club goalscoring record set by Robin van Persie.
Germany announced on Thursday that Havertz was included in their 23-man squad for Nations League fixtures against Bosnia-Herzegovina on October 11 and the Netherlands on October 14.
However, Die Mannschaft have since revealed that the 25-year-old will now miss both fixtures "due to knee problems".
Havertz to miss Germany matches due to injury
A statement posed on X read: "Kai Havertz will miss the upcoming international matches against Bosnia and Herzegovina and the Netherlands due to knee problems."
Germany have confirmed that head coach Julian Nagelsmann has called up Mainz 05 forward Jonathan Burkardt in Havertz's place.
Havertz has earned a total of 53 caps for his country and has scored 19 goals, including his latest strike in a thumping 5-0 home win over Hungary in Germany's Nations League opener last month.
Burkardt, meanwhile, is yet to make his senior international debut for Die Mannschaft, although he has regularly represented his country from Under-15 to Under-21 level, making a total of 41 youth appearances and scoring 20 goals.
The 24-year-old has made a bright start to the new season at club level with Mainz, netting six goals in seven matches across all competitions, including a brace in Saturday's 3-0 win at St Pauli in the Bundesliga.
Havertz's withdrawal comes just two days after Germany confirmed that Bayern Munich's Jamal Musiala will not be available this month "due to hip problems", with uncapped Jamie Leweling from Stuttgart called up in his place.
Who else is in Nagelsmann's 23-man squad?
Burkardt and Leweling are two of six uncapped players named in Nagelsmann's 23-man squad along with Borussia Monchengladbach forward Tim Kleindienst and goalkeeper trio Alexander Nubel, Oliver Baumann and Janis Blaswich.
Nagelsmann is tasked with selecting a new first-choice shot-stopper following Manuel Neuer's decision to retire from international football in August.
Red Bull Salzburg's Blaswich is one of three players returning to the senior squad along with Real Madrid defender Antonio Rudiger and Bayern's Serge Gnabry, the latter of whom is named in a national team squad for the first time in 11 months.
New captain Joshua Kimmich is the most-capped player (93) in Nagelsmann's squad, while highly-rated Bayern midfielder Aleksandar Pavlovic is the youngest player (20) selected.
Three players who have been omitted from this month's squad and who were involved in September are Marc-Andre ter Stegen - who is sidelined with a serious knee injury - Emre Can and Maximilian Beier.
Germany's 23-man squad in full:
Goalkeepers: Oliver Baumann (Hoffenheim), Janis Blaswich (Red Bull Salzburg), Alexander Nubel (Stuttgart)
Defenders: Waldemar Anton (Borussia Dortmund), Benjamin Henrichs (RB Leipzig), Joshua Kimmich (Bayern Munich), Robin Koch (Eintracht Frankfurt), Maximilian Mittelstadt (Stuttgart), David Raum (RB Leipzig), Antonio Rudiger (Real Madrid), Nico Schlotterbeck (Borussia Dortmund), Jonathan Tah (Bayer Leverkusen)
Midfielders: Robert Andrich (Bayer Leverkusen), Chris Fuhrich (Stuttgart), Pascal Gross (Borussia Dortmund), Jamie Leweling (Stuttgart), Alexander Pavlovic (Bayern Munich), Angelo Stiller (Stuttgart), Florian Wirtz (Bayer Leverkusen)
Forwards: Serge Gnabry (Bayern Munich), Deniz Undav (VfB Stuttgart), Tim Kleindienst (Borussia Monchengladbach), Jonathan Burkardt (Mainz 05)