The route passes through or close to the towns of Portsmouth, Waverly, Chillicothe, Grove City, and Columbus.

SR 104 is an original state highway with two parts: One from Portsmouth to Waverly, and one from Chillicothe to Columbus.

In March 1951, the Ohio Department of Highways converted an 8+1⁄2-mile-long (13.7 km) section of SR 104 south of Columbus into a test strip for traffic signs.

[2] The department abandoned the experiment four days after it started, after the signs attracted unexpected controversy and curious onlookers who posed a hazard.

[3][4] The experiments eventually led to the Vienna Convention on Road Signs and Signals, which was adopted in many countries but not the United States.