Virginia State Route 253 (SR 253) is a primary state highway in the U.S. state of Virginia. Known as Port Republic Road, the state highway runs 12.18 miles (19.60 km) from U.S. Route 11 (US 11) in Harrisonburg east to US 340 near Port Republic. SR 253 is a northwest–southeast highway that connects Harrisonburg with Cross Keys and Port Republic in southeastern Rockingham County. The state highway also provides access to portions of James Madison University on either side of Interstate 81 (I-81).

SR 253 begins at an intersection with US 11 (Main Street) south of downtown Harrisonburg and south of the campus of James Madison University. The state highway heads southeast as a four-lane undivided highway that intersects Bluestone Drive, which heads north to the campus and Bridgeforth Stadium and Zane Showker Field, just before meeting I-81 at a diamond interchange. SR 253's next intersection is with Forest Hill Road, which leads to the James Madison University Convocation Center, the Edith J. Carrier Arboretum, and the rest of the portion of James Madison University east of I-81. South of the university, the state highway becomes two lanes to the southern city limit of Harrisonburg. At the boundary between the independent city and Rockingham County, SR 253 expands to a four-lane divided highway. South of SR 704 (Boyer Road), the state highway becomes two lanes again and the surroundings transition from suburban to rural. SR 253 intersects SR 276 (Cross Keys Road) a short distance northeast of the village of Cross Keys. The state highway crosses the North River into the village of Port Republic, then exits the village by crossing the South River just west of the confluence of the two rivers to form the South Fork Shenandoah River. SR 253 has a grade crossing of Norfolk Southern Railway's Roanoke District before reaching its eastern terminus at US 340 (East Side Highway).