The 25-year-old was rushed to hospital having being helped off in obvious distress after twisting his left ankle just before the half time break in a challenge.
"I don't know yet what it is, we have to wait," said concerned Germany coach Joachim Löw.
"You could see the foot was swollen and I hope it's not a ligament (injury)."
Andre Schürrle gave the hosts a second-half lead and although Armenia's Henrikh Mkhitaryan converted a penalty, the floodgates opened as Germany scored five goals in the final 17 minutes.
Goals by Lukas Podolski, Benedikt Höwedes and Mario Götze, who scored twice, did the damage to floor minnows Armenia.
"We looked fresher and we took the tempo up in the second-half, but we still need a few good days training in Brazil," said Löw.
Replacement Miroslav Klose, who turns 36 on Monday, made history when he headed home their fourth to become Germany's all-time top scorer.
Klose netted his 69th goal for Germany on his 132nd appearance to finally break Gerd Müller's previous mark of 68 goals in 62 matches for West Germany.
"The goal record, of course, means a lot to me, but it was more important for us to be in form," said Klose.
"When we play as well as we did in the second-half, then we create plenty of chances and I'll score goals."
Both captain Philipp Lahm and his deputy Bastian Schweinsteiger played in Mainz after enforced injury breaks, but Reus' knock is a concern.
"Marco has been in great form and a bad injury would be very bitter," admitted Lahm.
Armenia squandered a golden early chance when Borussia Dortmund's Mkhitaryan played a great pass, but Gevorg Ghazaryan could not get his shot away and the opportunity went begging.
At the other end, his Dortmund team-mate Reus combined with Thomas Müller, who was playing up front as Germany's 'false nine', but his shot was cleared by defender Hrayr Mkoyan as it rolled towards the empty net with 13 minutes gone.
Reus' injury put a dampener on the first-half, but Germany got the break-through they needed when his replacement Podolski supplied a superb cross on 52 minutes which Chelsea's Schuerrle converted.
Armenia pulled a goal back when Kevin Grosskreutz conceded a penalty after a foul on Mkhitaryan less than a minute after coming on.
Germany went ahead three minutes later as Podolski fired home after a good pass from replacement Mesut Ozil on 72 minutes.
Schalke's left-back Höwedes grabbed the third when he followed up and netted his own saved shot on 73 minutes, then Klose made history with a header four minutes later as the floodgates burst.
Podolski looks to have played himself into Löw's starting line-up for Germany's World Cup opener on June 16th against Portugal.
He provided his second assist when he thread a superb pass through for Goetze to slid home Germany's fifth as Löw got the win he wanted before heading to Brazil.