Zoo staffers had put the 5-year-old male, named Edgar, with the 7-year-old female, Lina, in the hope the big cats would mate.
Instead, Edgar grabbed Lina by the throat and mauled her. Zookeepers tried to save her, but the female leopard died.
"For us it is emotional because we've never had this happen in the 30-plus years of my history here. But the species, it is an even bigger loss. This may be one of the world's most endangered cats. And to lose one of the most important breeding females is just devastating," said Zoo Director Scott Mitchell.
At this point, it is not clear what will happen to the male leopard, WSEE said.
The Amur leopard is the most endangered member of the cat family, according to the zoo's website.
Amur leopards are native to Korea, Manchuria and Siberia. Males weigh between 80 and 190 pounds and females weigh 60 to 130 pounds.