View west from the east end of SR 280 at US 33 in Massanetta Springs
SR 280 begins at a four-legged intersection with SR 42 (High Street) on the western edge of the independent city of Harrisonburg. The west leg of the intersection is unnumbered Erickson Avenue, which is the same name the state highway takes as it heads southeast as a four-lane divided highway. SR 280 intersects the Elkton–Dayton rail line of the Chesapeake Western Railway at grade, curves around a subdivision as an undivided highway, and regains a median before it intersects US 11 (Main Street). The state highway continues southeast as Stone Spring Road, which crosses over Black Run and the Harrisonburg–Pleasant Valley rail line of the Chesapeake Western Railway. SR 280 leaves the city limits of Harrisonburg and enters unincorporated Rockingham County shortly after it crosses over I-81 with no access. The highway curves east before its junction with SR 253 (Port Republic Road). SR 280 continues east through the unincorporated community of Massanetta Springs until it reaches its eastern terminus at US 33 (Spotswood Trail) south of Harrisonburg.
The city of Harrisonburg maintains SR 280 within the city limits. The Virginia Department of Transportation maintains the highway in Rockingham County.