The route begins at US 98/319 in Green Point, a rural community east of Eastpoint on the Gulf of Mexico in Franklin County, Florida.

Just around the intersection of NF Road 180, SR 65 curves to the northeast, where from here it spends the rest of its journey through the forest running from southwestern to northeastern Liberty County.

Curving straight north in front of a cemetery, SR 65 enters Hosford, Florida where it continues on this trajectory for more than four blocks.

Eventually this trajectory too shall end as it crosses the very Apalachicola Northern Railroad line it followed since Buck Siding.

The rest of the way, SR 65 continues to wind towards the northeast as it crosses the Liberty-Gadsden County Line, and adopts the name Hosford Highway.

Originally, SR 65 was co-signed with US 90 to Quincy, then north alone to the Georgia border, where it becomes State Route 241.

These include a county extension of a former segment of SR 65, and several suffixed alternate routes, many of which are duplicates of one another.

As Attapulgus Highway, the route winds around the outskirts of Quincy before curving primarily towards the northeast.

The route runs west from CR 65A then curves northwest to the Florida-Georgia State Line.

Unlike nearby CR 65A however, the name of the street changes to Betts Community Road upon crossing the border.

In fact, there's very little evidence it even connects to a suffixed alternate of these routes, other than the possibility of a hidden concurrency with State Road 267 towards southern CR 65B.

The road begins at SR 267 at the Wetumpka Volunteer Fire Department, and runs southeast through the Bear Creek Recreational Area of Lake Talquin State Park.