Zoo officials say the vulture flew the coop after a restrictive band on its wing broke Thursday, The (Jacksonville) Florida Times-Union reported.
Zoo staff tracked the bird to a tree on the grounds, but were unable to recapture it before it flew out of the site.
Officials from the zoo say they can't remember a bird ever escaping from the zoo before.
"It was a real hunt to get to him before he could fly out," but they couldn't, said zoo spokeswoman Gina Stiles.
The vulture, named Hodari, arrived at the Jacksonville Zoo in 2006 from the National Aviary in Pittsburgh. Zoo officials asked birdwatchers to contact the zoo if the bird is spotted, the newspaper said. Although he is not aggressive and does not pose a threat to people or animals, zoo officials say he should not be approached by the public.