Pennsylvania Route 641 (PA 641) is a state route located in Central Pennsylvania in the United States. The route is 57 miles (92 km) long from U.S. Route 522 in Shade Gap to U.S. Route 11 and U.S. Route 15 in Camp Hill. PA 641 carries names like Trindle Road, Forge Hill Road, Newburg Road, Main Street, Newville Road, Green Spring Road, Carlisle Road, High Street, and Timmons Road.

PA 641 begins at an intersection with U.S. Route 522 in Shade Gap. 800 feet (240 m) east of US 522, PA 641 intersects Pennsylvania Route 35. East of PA 35, PA 641 continues towards the southeast. When PA 641 crosses the Tuscarora Mountain, it has multiple S-curves. At the county line, PA 641 makes a sharp loop towards the south.

Upon entering Franklin County, PA 641 becomes Spring Run Road and makes a sharp turn towards the north. Then, PA 641 curves towards the southeast. In Spring Run, PA 641 intersects Pennsylvania Route 75. PA 641 continues east of PA 75 towards the south as Spring Run Road. In Fannett Township, PA 641 makes a 90 degree angle turn passing under Interstate 76 (Pennsylvania Turnpike). Then 380 feet (120 m) east of the I-76 underpass, PA 641 intersects its truck route and PA 641 continues east as Timmons Road. PA 641 Truck has an arch around the Pa Turnpike and then comes back to PA 641. In Lurgan Township, PA 641 crosses Blue and Kittatinny Mountains. PA 641 also becomes Forge Hill Road and has a short concurrency with Pennsylvania Route 997. East of PA 997, PA 641 continues towards the east as Newburg Road.

After crossing the Laughlin Run, PA 641 enters Cumberland County. In Newburg, PA 641 becomes Main Street and has a short concurrency with Pennsylvania Route 696. PA 641 continues as Newburg Road. In North Newton Township, PA 641 becomes Green Spring Road. In the borough of Newville, PA 641 becomes Main Street and intersects Pennsylvania Route 233. East of Newville, PA 641 continues as Carlisle Road. Then PA 641 shifts towards the northeast. In West Pennsboro Township, PA 641 becomes Newville Road and parallels the Pa Turnpike. In North Middleton Township, PA 641 intersects the northern terminus of Pennsylvania Route 465. Upon entering Carlisle, PA 641 makes a right turn towards the south to become Orange Street. Then PA 641 begins a concurrency with U.S. Route 11 (High Street). Then US 11/PA 641 begin a wrong-way concurrency with Pennsylvania Route 74 (College Street). At the center of Carlisle, US 11 leaves the concurrency while PA 74/PA 641 meet Pennsylvania Route 34. East of US 11/PA 34, PA 74/PA 641 continue as High Street. In the eastern part of Carlisle, PA 74 heads southeast and splits from PA 641. To I-81 north drivers have to continue on PA 641 and to I-81 south drivers have to take PA 74. East of Carlisle, PA 641 intersects Interstate 81 north only at exit 49. East of I-81, PA 641 continues as Trindle Road. A parking lot for Appalachian Trail access is at Stony Ridge. West of Mechanicsburg, PA 641 intersects the eastern terminus of Pennsylvania Route 174 and east of PA 174, PA 641 passes over I-76/Pa Turnpike. In Mechanicsburg, PA 641 becomes Main Street and has a concurrency with Pennsylvania Route 114. In Camp Hill, PA 641 interchanges with U.S. Route 11 and Pennsylvania Route 581. PA 641 has access only to US 11 north and PA 581 east. PA 641 terminates (ends) at an intersection with US 11 and U.S. Route 15.

Pennsylvania Route 641 Truck is an 8-mile (13 km) long truck route in rural Franklin County, Pennsylvania. While much longer in terms of distance, it allows heavy vehicles to bypass an especially winding stretch of mountain highway. The alternate route parallels a stretch of the Pennsylvania Turnpike as Anderson Road, then descends over the range as Cool Spring Road. While the truck route still features a relatively steep grade, it is less than that of its parent route and features significantly less traffic.