The blazes -- which have been burning near the coastal township of Port Macquarie since Monday -- have destroyed more than 2,000 hectares (4,492 acres) of koala heartland, CNN affiliate 9News reported.
Local animal experts Koala Hospital Port Macquarie said the fires have "decimated" the area, which is a key habitat and breeding ground for the creatures.
As few as 43,000 of the marsupials are left in the wild in Australia, according to the Australian Koala Foundation (AFK).
Listed by the Australian government as "vulnerable," the tree-dwelling creatures are in serious decline due to habitat destruction, bushfires, road accidents and dog attacks, the AFK says.
"So far over two thirds of the current footprint of the fire is prime koala habitat (or was)," Koala Hospital Port Macquarie said in a statement on Facebook.
"Crunching the numbers based on koala survey work of the whole LGA (local government area) -- it is looking like conservatively based on a 60% mortality that 350 plus koalas have died in the last three days in this fire," the hospital added.
There are 72 bush and grass fires ablaze in the state -- with 38 fires still to be contained, 9News reported on Wednesday.