The Borussia Dortmund star was clearly in pain and had to be substituted after twisting his left ankle, with his participation at the World Cup now thrown into doubt
The Borussia Dortmund player had to be helped from the field by medics after suffering an apparent ankle injury just a minute before the end of the first half.
Reus had been left screaming on the ground in agony following a heavy challenge from Armenia midfielder Artur Yedigaryan and had to be replaced by Lukas Podolski.
The 25-year-old was immediately taken to hospital to undergo an MRI scan, the results of which will determine whether or not he will be fit to play in the World Cup, which kicks off in under a week.
Reus, who has 21 caps for Germany, had been considered to be a certain starter for his country's World Cup opener against Portugal.
While the results of his scan are yet to come through, the mood in the camp appears to be negative with coach Joachim Low and a number of key players indicating that they expected to hear bad news.
"Reus is in the hospital undergoing a MRI scan," the coach told ZDF.
"Now we have to wait for the results. In such a situation you have many thoughts running through your head.
"During half-time we saw that his foot had swollen. I hope that he hasn't suffered a ligament injury and everything is OK, but it did look bad."
Toni Kroos echoed his coach's view that the initial signs were not good when he was asked what he had seen of the Reus injury.
"It did not look good at first glance," he said. "I hope he will be fit and ready because we need him."
Under Fifa rules, Low can call up a replacement for any injured player up to 24 hours before his side's first match at the tournament.
The fitness blow for Reus overshadowed a spectacular victory for Germany, who scored six times in the second half as they powered to victory, with veteran Miroslav Klose amongst those finding the net to become his country's all-time top goalscorer.