State Route 66 is a north–south state highway in the northwestern portion of the U.S. state of Ohio. Its southern terminus is at U.S. Route 36 (US 36) in Piqua, and its northern terminus is at US 20 in Fayette. South of Defiance it generally follows the route of the former Miami and Erie Canal.

The Miami and Erie Canal was a 274-mile (441 km) canal that ran from Cincinnati to Toledo, Ohio, creating a water route between the Ohio River and Lake Erie. Construction on the canal began in 1825 and was completed in 1845 at a cost to the state government of $8 million. At its peak, it included 19 aqueducts, three guard locks, 103 canal locks, multiple feeder canals, and a few man-made water reservoirs. The canal climbed 395 feet (120 m) above Lake Erie and 513 feet (156 m) above the Ohio River to reach a topographical peak called the Loramie Summit, which extended 19 miles (31 km) between New Bremen, Ohio to lock 1-S in Lockington, north of Piqua, Ohio. Boats up to 80 feet long were towed along the canal by mules, horses, or oxen walking on a prepared towpath along the bank, at a rate of four to five miles per hour.