Die Schwarzgelben centre-back picked up a foot injury during his side's 1-1 draw with Hannover and will be unavailable for the clashes with Ireland and Sweden
The 23-year-old had picked up a hip injury during his club's 1-1 draw with Manchester City last week, but recovered in time to start Sunday's match against Hannover, which ended in the same result.
However, he lasted just 45 minutes at the AWD Arena and was forced off at half-time, and it has now been confirmed by the Ruhr outfit that he suffered a bruised foot and will be out of action for around two weeks.
Another Dortmund star who faces a spell on the sidelines is Jakub Blaszczykowski, who will be out for around six weeks with a partial tear of a joint in his left knee.
Finally, midfielder Sven Bender and Sebastian Kehl have been ordered not to train with their side for the next four days after their exertions.
Germany travel to Republic of Ireland on Friday, looking to make it three wins from three in qualifying for Brazil 2014, and host Sweden four days later.
Low has already moved to call up Hamburg skipper Heiko Westermann in Hummels' stead, and will also be able to call upon the services of Per Mertesacker, Benedikt Howedes, Holger Badstuber and Jerome Boateng.
Dortmund's first match after the international break is the Ruhr derby against Schalke at home on October 20, with the German champions entertaining Real Madrid the following Tuesday.