Pocock had been due for a return to action at Twickenham after recovering from knee ligament damage.
But scans confirmed on Monday night that the openside flanker had suffered a calf strain, ruling him out of the game.
Australia will also be without lock Kane Douglas, who played in Saturday's 33-6 defeat to France but has developed a knee injury.
The Wallabies' second row stocks will be hit further on Wednesday if lock Rob Simmons is found guilty of the dangerous tip tackle he was cited for after the Paris match.
Douglas was urged by his family to play against France despite the news that his mother, Trish, had suffered a stroke on the flight from Australia on Friday.
While still in hospital in London, Mrs Douglas is listed as being in a comfortable condition.