Pennsylvania Route 66 (PA 66) is a 139 miles (224 km) long state highway in Western Pennsylvania. Its northern terminus is at U.S. Route 6 in Kane. Its southern terminus is at US 119 (just east of Interstate 70) near New Stanton. West of Greensburg, PA 66 becomes the tolled Amos K. Hutchinson Bypass, a part of the Pennsylvania Turnpike System. The Bypass runs between U.S. Route 119 and U.S. Route 22.

PA 66 begins in New Stanton at a cloverleaf interchange with US 119, Interstate 70, and Interstate 76 (Pennsylvania Turnpike). Exit 1 is for Arona Road, where no tolls are collected. Exit 4 is the first toll exit. Exit 4 is located in Hempfield Township and PA 66 interchanges with Pennsylvania Route 136 at exit 4. 1 mile (1.6 km) north of PA 136, PA 66 reaches the Hempfield Toll Plaza. Southeast of Jeannette, PA 66 interchanges with U.S. Route 30 at exit 6. Exit 8 is located 1 mile (1.6 km) east of Jeannette and PA 66 interchanges with Pennsylvania Route 130. At exit 9, PA 66 interchanges with Pennsylvania Route 66 Business the former routing of PA 66. At exit 12, PA 66 interchanges with the northern terminus of PA 66 Business. At exit 14, PA 66 meets U.S. Route 22 at a single-point urban interchange. North of US 22, PA 66 continues north at-grade.

Tolls are collected once during travel on the road, either at the mainline toll barrier, or at the exit or entrance point, depending on the possibility of reaching the mainline toll barrier during travel. No toll is charged for travel between exits 0 and 1 or between exits 12 and 14. Tolls are paid either by cash or E-Z Pass. At the mainline toll barrier, a manned full service lane exists. For most exit ramp tolls, exact coins are required; however some automatic toll collection machines accept paper money and give change. All toll collecting machines give receipts.

The highway was built primarily to eliminate the need for trucks traveling to northwestern Pennsylvania via U.S. Route 119 and PA 66 from having to travel through downtown Greensburg. When the highway first opened, many trucks avoided the bypass due to the toll along the turnpike. However, turn restrictions in Downtown Greensburg forced many trucks to use the bypass.

North of the Amos K. Hutchinson Bypass, PA 66 enters Salem Township as Sheridan Road. In Delmont, PA 66 is called Sheridan Road. In Washington Township, PA 66 passes west of Beaver Run Reservoir. In the village of Mamont, PA 66 intersects Pennsylvania Route 286. In the village of Poke Run north of PA 286, PA 66 intersects the eastern terminus of Pennsylvania Route 366. Then PA 66 intersects Pennsylvania Route 380, PA 380 west heads for downtown Pittsburgh. South of Oklahoma, PA 66 intersects the southern terminus of Pennsylvania Route 356. In the village of Paulton, PA 66 intersects the southern terminus of Pennsylvania Route 66 Alternate. PA 66 Alternate goes into Vandergrift and PA 66 goes into Apollo. In Oklahoma, PA 66 meets the northern terminus of Pennsylvania Route 819. In downtown Oklahoma, PA 66 turns to the east and crosses the Kiskiminetas River.

After crossing the Kiskiminetas River, PA 66 has entered Armstrong County and begins a concurrency with Pennsylvania Route 56 in Apollo. As they began their concurrency, PA 56/PA 66 were called Warren Avenue in Apollo. As PA 56/PA 66 enter the boro of North Apollo they are paralleling the Kiskiminetas River. In the village of North Vandergrift, the concurrency between PA 56 and PA 66 ends when PA 66 intersects PA 66 Alternate and PA 56 and PA 66 ALT begin their own concurrency into Vandergrift. As PA 66 continues to parallel the Kiskiminetas River, it is called Lincoln Avenue. While paralleing the Kiskiminetas River, PA 66 has snake like curves. In Leechburg, PA 66 becomes Market Street, 3rd Street, and Pershing Avenue. As PA 66 exits Leechburg it is not paralleling the Kiskiminetas River. In Bethel Township, PA 66 meets the northern terminus of PA 66 Alternate. In Ford City, PA 66 becomes Main Street and intersects the northern terminus of Pennsylvania Route 128 at an "Y" intersection. Southeast of Kittanning, PA 66 begins a concurrency with U.S. Route 422 and Pennsylvania Route 28 at an interchange. At the next exit US 422 leaves the concurrency and PA 28/PA 66 continue north at-grade. In Rayburn Township, PA 28/PA 66 intersect the western terminus of Pennsylvania Route 85. PA 28/PA 66 continue towards the northeast without intersecting a route for more than 17 miles (27 km). In South Bethlehem, PA 28/PA 66 become Broad Street and meet the northern terminus of Pennsylvania Route 839. The route then crosses the Redbank Creek into Clarion County after spending 43 miles in Armstrong County.

After crossing the Redbank Creek, PA 28/PA 66 have entered Clarion County. In New Bethlehem, The concurrency between PA 28 and PA 66 ends when PA 66 leaves PA 28. North of PA 28, PA 66 becomes Wood Street and intersects the eastern terminus of Pennsylvania Route 861. In Clarion Township, PA 66 begins a concurrency with Interstate 80 at exit 64. Then I-80/PA 66 meet Pennsylvania Route 68 at exit 62. After crossing the Clarion River, PA 66 leaves I-80 at exit 60 (trumpet interchange). PA 66 continues north at-grade. In Paint Township, PA 66 intersects U.S. Route 322 as Paint Boulevard. PA 66 continues towards the north paralleling rail road tracks. In Farmington Township, PA 66 intersects Pennsylvania Route 36.

As PA 66 enters Forest County, PA 66 intersects the northern terminus of Pennsylvania Route 899. In Jenks Township, PA 66 enters Allegheny National Forest. As PA 66 enters Elk County, PA 66 has a 2 miles (3 km) concurrency with Pennsylvania Route 948. Northeast of PA 948, PA 66 becomes Kane-Russell City Road. PA 66 enters McKean County as Fraley Street. In Kane, PA 66 terminates (ends) at a "T" intersection with U.S. Route 6.

Cash $1.60, E-ZPass $1.33 for 2-axle vehicles

Pennsylvania Route 66 Alternate is an 11-mile (18 km) long alternate tract through Armstrong County, Pennsylvania. It leaves its parent route in Parks Township (North Vandergrift), avoiding several riverfront towns as it travels along a hilly, rural stretch, before rejoining mainline PA 66 in Bethel Township.

Pennsylvania Route 66 Business is an 8-mile (13 km) long business route in Westmoreland County, Pennsylvania, connected two fingers of suburbia located east of Pittsburgh. The highway was created when a mainline Route 66 was shifted onto a toll bypass. The route begins nearly a mile south of the original terminus of PA 66, at a juncture with U.S. Route 30 (which loops as a freeway around the city). It is cosigned with Pennsylvania Route 819 to the city center, before travelling on its own accord through several suburbanized miles. The route then becomes more rural, as it provides a free connection to the north-central edge of suburban Pittsburgh at Delmont.