Witsel suffered oral and facial injuries in a domestic accident over the weekend and has already undergone surgery at the Klinikzentrum Nord Hospital to repair the damage.
The 30-year-old played the full 90 minutes on Saturday as Dortmund walloped Fortuna Dusseldorf 5-0 at the Signal Iduna Park to move third on the league table but suffered the injury afterwards.
Witsel will therefore be missing in action when Dortmund, who are third in their UEFA Champions League group behind Barcelona and Inter Milan, host Slavia Prague on Tuesday to try and secure their place in the knockout stages.
The Belgium international will also miss crucial Bundesliga games against second-placed RB Leipzig, Mainz 05 and TSG Hoffenheim before the turn of the year.
"Witsel sadly will be out for the rest of this year," Dortmund coach Lucien Favre told a news conference ahead of Tuesday's Champions League match against Slavia Prague.
"But there is one positive thing: He's already back home. We can't change it now. It's a shame for him, a shame for us. He's one of the most important players for us."
"I was told about this yesterday morning," Favre added.
"We could not speak to him. He was in hospital."
The former Benfica and Zenit Saint Petersburg midfielder has played 21 times in all competitions for Dortmund this season and has scored three goals and provided three assists.