Low said on Wednesday that the 28-year-old, voted the best goalkeeper at last year's FIFA World Cup, will sit out the match at Kaiserslautern's Fritz Walter Stadion with a light infection of the meniscus in his knee as a precautionary measure.
His place will go to either Borussia Dortmund's Roman Weidenfeller or Hannover's Ron-Robert Zieler, but Neuer's injury boosts Australia's hopes of pulling off another upset after its 2-1 win in 2011, which was the Socceroos' first win over Germany at the fourth attempt.
The Bayern Munich shot-stopper is expected to play in this weekend's EURO 2016 qualifier away to Georgia, with Germany sitting second in its group behind leader Poland and level with Republic of Ireland and Scotland.
"We have decided that Manuel won't play on Wednesday, he has a light infection which will get better quickly with rest and we didn't want to risk him," explained Low.
"We haven't decided who will replace him against Australia, but there is no risk against Georgia.
"We wanted to give him the time to recover so that he will be fit."