The southern terminus of SR 278 is at US 50 approximately 4.75 miles (7.64 km) east of McArthur.

The highway's northern terminus is at the T-intersection it has with SR 595 nearly 5.50 miles (8.85 km) northwest of Nelsonville.

Established in the early 1930s, SR 278 primarily connects rural communities in Vinton, Hocking, and Athens Counties.

SR 278 travels through the large portions of the counties of Vinton, Hocking and Athens.

[3][4] In 1937, the highway was extended north from Zaleski, through Nelsonville up to its current northern terminus at SR 595.