Holding a four point lead at the top of Group J, Germany can sew up qualification for the World Cup by beating Romania in Hamburg on October 8, then away to North Macedonia in Skopje three days later.
In his 23-man squad, Flick recalled veteran Thomas Mueller, goalkeeper Marc-Andre ter Stegen and Matthias Ginter, but explained why he decided to rest Hummels, 32, who has a knee problem.
"We all know what qualities Mats has when he's 100 percent fit," Flick said of the 2014 World Cup winner.
Manchester City midfielder Ilkay Gundogan, Atalanta defender Robin Gosens and Dortmund defender Mahmoud Dahoud all miss out with injury, but there are places for promising teenagers Jamal Musiala and Florian Wirtz.
After sweeping aside Armenia 6-0 and Iceland 4-0 in last month's qualifiers, Flick wants further convincing displays in their next two games to book Germany's place at the World Cup finals.
"We have a four-point lead, we want to build on that and qualify as quickly as possible," he added.
Goalkeepers: Manuel Neuer (Bayern Munich), Bernd Leno (Arsenal/ENG), Marc-Andre ter Stegen (Barcelona/ESP)
Defenders: Matthias Ginter (Borussia Moenchengladbach), Thilo Kehrer (Paris St. Germain/FRA), Lukas Klostermann (RB Leipzig), David Raum (Hoffenheim), Antonio Ruediger (Chelsea/ENG), Nico Schlotterbeck (Freiburg), Niklas Suele (Bayern Munich).
Midfielders/Forwards: Karim Adeyemi (Red Bull Salzburg/AUT), Serge Gnabry (Bayern Munich), Leon Goretzka (Bayern Munich), Kai Havertz (Chelsea/ENG), Jonas Hofmann (Borussia Moenchengladbach), Joshua Kimmich (Bayern Munich), Thomas Mueller (Bayern Munich), Jamal Musiala (Bayern Munich), Florian Neuhaus (Borussia Moenchengladbach), Marco Reus (Borussia Dortmund), Leroy Sane (Bayern Munich), Timo Werner (Chelsea/ENG), Florian Wirtz (Bayer Leverkusen).