Just after the half-hour mark, the 33-year-old was forced off after rolling his ankle following a challenge from Schalke midfielder Florian Flick, before Youssoufa Moukoko scored the only goal of the game for Dortmund 12 minutes from time to secure a 1-0 Bundesliga win.
With Reus leaving the pitch in tears, there were concerns that the 48-cap Germany international - who has been hampered with injuries throughout his career - could miss the upcoming World Cup in Qatar.
Reus played three times at the 2018 World Cup, but he missed Germany's triumphant 2014 World Cup campaign after sustaining an ankle injury on the eve of the tournament.
However, Dortmund sporting director Sebastian Kehl has provided a reassuring update, confirming that Reus is only set to miss the next three to four weeks with ankle ligament damage.
"It looks as if the ligaments were injured," Kehl told SPORT1. "Of course, he was very disappointed and was in a lot of pain."
"It was a shock for us, too, but I can give a little 'all clear'. The examinations showed no fracture, just a lateral ligament injury at the ankle. [It is] not so difficult that the World Cup is in danger."
Germany head coach Hansi Flick initially included Reus in his 24-man squad for their upcoming UEFA Nations League fixtures against Hungary and England this month.
However, Flick has now replaced the Dortmund attacker with RB Leipzig full-back Benjamin Henrichs, who will be looking to add to his seven international caps.
Reus is expected to miss Dortmund's next three matches after the international break, including the Champions League trip to Sevilla on October 5 and the Bundesliga showdown with reigning champions Bayern Munich three days later.
Dortmund then have 10 more fixtures across all competitions in which Reus could return and build up his fitness and form ahead of Germany's first World Cup match in Group E against Japan on November 23.
Reus scored 13 goals and provided 19 assists in 41 appearances for Dortmund across all tournaments last season, and he has since recorded three goals and four assists in 10 games this term.
Flick still has plenty of attacking options at his disposal ahead of their final two League A Group 3 fixtures in the Nations League, with the likes of Leroy Sane, Serge Gnabry, Julian Brandt and Jonas Hofmann all set to battle for a place on the flanks.
Meanwhile, Timo Werner, Kai Havertz and Lukas Nmecha will likely compete with each other for a start as the central striker behind either Thomas Muller or Jamal Musiala.
Germany are scheduled to face group leaders Hungary at the Red Bull Arena on September 23, before taking on Euro 2020 finalists England at Wembley Stadium in their final match three days later.