The Germany midfielder's latest injury blow came as a result of a strong challenge from Paderborn midfielder Marvin Bakalorz during Saturday's 2-2 Bundesliga draw at the Benteler-Arena.
Reus has been plagued by injuries, one of which was ankle ligament damage which kept him out of the World Cup, and the 25-year-old is not expected to return until next year.
A statement on Dortmund's official website said: "Borussia Dortmund midfielder Marco Reus suffered a torn ligament in his right ankle in Saturday's Bundesliga game at SC Paderborn. The injury will rule the 25-year-old Germany international out for the rest of the year.
"Reus could return to training at the start of 2015 when BVB begin their preparations for the second half of the season."
The former Borussia Monchengladbach man had put Dortmund 2-0 on the stroke of half-time before suffering the injury midway through the second period.
Paderborn mounted a fightback to snatch a point, ensuring Jurgen Klopp's side are just one place and a point above third-bottom Werder Bremen.
Klopp was aggrieved that Bakalorz was not dismissed for the challenge on Reus.
"It was a horrific moment," the head coach said. "It's a red card. A draw in Paderborn isn't that dramatic, but the loss of Reus is harder to accept."
