State Road 64 extends from City Road 789 (former County Road 789) near the Gulf of Mexico in Holmes Beach on Anna Maria Island in Manatee County to US 27/US 98 in Avon Park in Highlands County. State Road 64 travels from west to east through the counties of Manatee, Hardee and Highlands. It is a mostly rural two-lane highway going through only two cities, Bradenton and Zolfo Springs. It crosses the Gulf Intracoastal Waterway as well as the Braden River, Lake Manatee, and the Myakka River. East of Avon Park, a bi-county extension runs northeast into Polk County which runs through Lake Wales Ridge State Forest and terminates at the Avon Park US Air Force Base. It is designated as the Florida Cracker Trail from Bradenton to the Hardee County Line.

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