According to the Nashville zoo authorities, more than 28 cubs have been born in 17 litters since 2009.
But this is the first time a cub was conceived through artificial insemination with cryopreserved sperm, media reports said.
On Thursday, a tweet from the Zoo said, "Nashville Zoo & Smithsonian make history with birth of clouded leopard!"
The father, named Hannibal, lives at the National Zoo in Washington. The mother, named Tula, was born and raised at the Nashville Zoo.
Clouded leopards are listed as "vulnerable" and protected in most range countries. However, exact data on the number of these cats existing in the world are not known.