The cow came from a dairy farm in Tulare County, the nation's No. 1 dairy-producing county.
The USDA didn't elaborate on the cow's symptoms other than to say it was "humanely euthanized after it developed lameness and became recumbent." Outward signs of the disease can include unsteadiness and incoordination.
The animal was never destined for the meat market and there is no risk to the food supply. Officials say the cow developed an "atypical" form of mad cow disease, or bovine spongiform encephalopathy, from a random mutation, something that scientists know happens occasionally. Somehow, a protein the body normally harbors folds into an abnormal shape called a prion, setting off a chain reaction of misfolds that eventually kills brain cells.
Routine testing at a transfer facility showed that the dead cow had mad cow disease. It was the fourth case of mad cow disease ever discovered in the U.S.
The Associated Press contributed to this report.