Asian elephant Man Jai, nine, died after being diagnosed with the incurable disease Elephant Endotheliotropic Herpesvirus (EEHV), the zoo said.
The disease only affects elephants and usually the creatures naturally carry the virus without symptoms, the zoo said.
Occasionally infection can "reactivate" and usually kills, the zoo said.
Vets battled to save Man Jai after he became ill, the zoo said, but it was not possible.
"On Monday his specialised keepers, who monitor the herd closely and frequently for signs of this disease, noticed swelling in his neck and uncharacteristic lethargy," the zoo said.
"Man Jai was immediately tested by Melbourne Zoo veterinarians for EEHV, with blood tests confirming a positive diagnosis and urgent anti-viral treatment being administered.
"Despite Melbourne Zoo's veterinary and keeper expertise, and around-the-clock care, Man Jai tragically lost his life to the virus in the early hours of this morning.
"Melbourne Zoo staff, volunteers and, in particular, Man Jai's keeper team, many of whom have cared for him since he was born, are devastated by the loss."
Director of Melbourne Zoo Sheri Horiszny said many visitors will have special memories of Man Jai, who was born in December 2013.
"Man Jai was playful, joyful and adored by his herd and all who knew him," Horiszny said.
"We are deeply affected by the loss of such a spectacular elephant, and we will all miss him so much.
"It's hard to find the words to share how difficult this is for all the keepers who looked after him for his whole life and worked tirelessly to try to save him.
"Our focus now is to continue closely monitoring the rest of the elephant herd, which is also grieving."
Melbourne Zoo Trail of the Elephants is closed to visitors after the sad death.
Asian Elephants can be found in Sri Lanka, Laos, Thailand, Burma, China, Malaysia, India, Indonesia, Vietnam and Cambodia.
There are fewer than 53,000 remaining in Asia, and the wild population is decreasing.
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2023-08-24 09:22:57Z
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