The Germans beat Scotland 2-1 but all eyes were on Reus in the hours after the game.
Recently appointed captain at Borussia Dortmund, Reus walked off the pitch unassisted after the clash with defender Charlie Mulgrew resulted in a yellow card for the Scotsman.
But tests on Monday showed that he had torn his left lateral collateral ligament and strained his tarsal ligaments, taking him out of action for four weeks.
It was Reus' first appearance since his previous injury forced him out of the World Cup-winning national squad during the final qualifying game against Armenia in June. He had only just returned to form, scoring the first goal in a recent 3-2 victory for Dortmund over Augsburg.
Terrible for Marco Reus: The BVB and Germany star had to be substituted off with another apparent injury https://t.co/4kjWi3Y0GQ— Bleacher Report UK (@br_uk) September 7, 2014
Germany lost 4-2 against Argentina in a friendly on Wednesday but a goal in each half from Bayern Munich attacker Thomas Müller in Dortmund ensured they won their first competitive fixture since the World Cup.
Scotland delivered a spirited performance and they were rewarded for a positive second-half approach when winger Ikechi Anya raced clear to equalise on 66 minutes.
But the visitors failed to clear a corner four minutes later and Müller capitalised to thump home his 24th international goal.
“I'm totally happy that we've managed three points,” said Germany coach Joachim Löw. “That was my one expectation of the team, to win this game and make a good start on the qualification.
“This game was going to be hard, the Scots didn't have anything to lose.”
Müller's winner denied Gordon Strachan's side what would have been a precious point in a group that also includes the Republic of Ireland, Poland, Georgia and Gibraltar.
"At 1-1, I genuinely believe we can win the game at that point," Strachan said.
"The longer the game we went on, the more of a threat we got. We really should be proud. All we have to do is work on the first 20 minutes. Get that sorted out and we'll be fine. We'll be good."
In midfield, Germany were missing new captain Bastian Schweinsteiger, Real Madrid's Sami Khedira and Arsenal's Mesut Özil, while at the back Jerome Boateng returned in defence.
With Philipp Lahm having retired after the World Cup, Hoffenheim's Sebastian Rudy surprisingly earned his third cap at right-back.
Scotland were captained by Manchester United midfielder Darren Fletcher and the visitors also included in-form Everton striker Steven Naismith as they sought to beat Germany in a competitive fixture for the first time.