The elusive cat was first placed on the endangered species list in 1973.
The Fish and Wildlife Service has determined there are not enough eastern cougars remaining to maintain breeding populations.
There have been no sightings of the cougar in the 21 states where it once lived.
The US Fish and Wildlife Service declared the eastern cougar officially extinct Wednesday, even though the big cat is believe to have first disappeared in the 1930s.
The eastern cougar is often called the "ghost cat" because it has been so rarely glimpsed in northeastern states in recent decades. It was first placed on the endangered species list in 1973.
"The US Fish and Wildlife Service conducted a formal review of the available information and... concludes the eastern cougar is extinct and recommends the subspecies be removed from the endangered species list," a statement said.
"Only western cougars still live in large enough numbers to maintain breeding populations, and they live on wild lands in the western United States and Canada."
The US agency asked for input about the eastern cougar, and determined from the 573 responses it received that any sightings in the area were actually of other types of cougars.
Of the 21 states in the historical range of the cats, "no states expressed a belief in the existence of an eastern cougar population," it said.
The service's lead scientist for the eastern cougar, Mark McCollough, said the animal has likely been extinct since the 1930s.