The highway serves to connect the unincorporated community of Paterson to the county seat Prosser.

After the highway resumes its northerly course it climbs into the Horse Heaven Hills, gaining a passing lane through the uphill segments,[1] before finally terminating at SR 22 in south Prosser.

[2] Every year the Washington State Department of Transportation (WSDOT) conducts a series of surveys on its highways in the state to measure traffic volume.

[3] The roadway on its current alignment has existed since at least 1926,[4] however there are records of a road between Paterson and Prosser since 1906.

[8] High winds have forced the closure of SR 221 in 2003,[9] 2004,[10] and 2005 due to large amounts of dust being blown around, causing visibility to drop to almost zero through the Horse Heaven Hills.