The case is in a seven-year-old Quarter Horse gelding in Jackson County, Missouri.
The United States Department of Agriculture reported the case to the World Organisation for Animal Health (OIE) on June 11, a day after the horse returned a positive test for the disease.
Dr John Clifford, deputy administrator for the Animal and Plant Health Inspection Service, said the gelding was purchased six months ago and has been housed on the Jackson County premises since.
"In addition to the affected horse, there are 63 other animals on the property, including horses, ponies and mules," he said.
"Of these, 44 animals are stabled, 18 are on a common pasture, and one is on an isolated pasture."
The infected horse first showed clinical signs consistent with equine piroplasmosis on June 1.
It was taken to a veterinary medical hospital in Kansas for an acute illness consistent with infection by a blood-born pathogen. The horse was quarantined and the infection later confirmed.
The disease is caused by a protozoa, Theileria equi, which can be carried by certain kinds of ticks. The ill animal and others on the affected premises were examined for ticks. No ticks were found.
Clifford said the Animal Plant Health Inspection Service, in conjunction with the Missouri Department of Agriculture, is conducting a comprehensive investigation of the event.
While equine piroplasmosis is a tick-borne disease, it can also be spread by contaminated needles.
Its symptoms include weight loss, jaundice, fever and anaemia.
The United States routinely screens all imported horses for piroplasmosis.
The last reported occurrence of the disease in the US was in February in Florida. That investigation involved the quarantining of 25 properties and the tested of more than 200 horses. Horses found to be infected with the disease were euthanized.