They say they found neglected cats, rabbits, birds, tortoises, snakes and other animals living in filth in a house in Brookhaven.
They say the animals were surrounded by their own urine and feces, and covered in vermin.
Some of the animals were also suffering from untreated medical conditions.
"When ASPCA responders arrived on the property, it was clear immediate intervention was necessary to remove hundreds of neglected animals from the inhumane and brutal conditions they were subjected to and provide them with expert care," Matt Bershadker, ASPCA President and CEO said.
The animals are being taken to shelters and rescue groups across New York.
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