The Austrian star picked up the knock during the club's recent defeat to RB Leipzig, and the news has hit the team hard.
Sky have reported that Sabitzer's injury will keep him off the pitch for several weeks, with the 30-year-old now facing a race against time to regain fitness.
"Marcel suffered a knee injury in Leipzig and will undergo rehabilitation training over the next four weeks," Dortmund confirmed in a statement posted on X.
The setback means he'll miss Austria's crucial Nations League play-off against Serbia, as well as Dortmund's blockbuster clashes with Bayern Munich and FC Barcelona in the Champions League.
Sabitzer's absence is a major blow for Dortmund, who leaned heavily on his versatility and drive during last season's run to the Champions League final.
After a rocky start to the current campaign under former boss Nuri Sahin, the midfielder had found his groove under new head coach Niko Kovac.
"He's been a key figure for us," Kovac had said earlier this season, praising Sabitzer's ability to influence games from multiple positions.
With tough fixtures looming, Dortmund will need to dig deep to fill the void left by their sidelined star.