It is 19.01 miles (30.59 km) long and runs north–south, entirely within Hood River County.

OR 281 begins at an intersection with US 30 and OR 35 at Hood River and heads south, intersecting OR 282 five miles (8 km) south of Hood River.

OR 281 continues south through Winans, Dee, and Trout Creek to Parkdale.

At Parkdale, OR 281 turns northeast for two miles (3 km) to the community of Mount Hood, where it ends at an intersection with OR 35.

The entire route is in Hood River County.