It is a divided limited-access highway in the metropolitan Evansville area, where it is part of the Lloyd Expressway, and also between the unincorporated communities of Yankeetown and Hatfield.

For the most part, however, State Road 66 is undivided rural highway following the Ohio River, and a large portion of its route (from just east of Newburgh to State Road 62 at Sulphur) carries the designation of the Ohio River Scenic Byway.

In the spring of 1983, buildings in the expressway's path began coming down and construction officially started on July 29, 1983.

Motorists endured five years of detours and construction as the expressway was built through the heart of the city.

As of March 2009, work was well underway on the segment from State Road 261 to the Newburgh Lock & Dam.