The southernmost 13.7 miles (22.0 km) of the route is a controlled-access toll road named the Amos K. Hutchinson Bypass and is signed as PA Turnpike 66, a part of the Pennsylvania Turnpike System serving as a bypass of Greensburg.

North of the Amos K. Hutchinson Bypass, PA 66 enters Salem Township as Sheridan Road.

In Washington Township, PA 66 passes west of Beaver Run Reservoir.

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.

In downtown Oklahoma, PA 66 turns to the east and crosses the Kiskiminetas River.

After crossing the Kiskiminetas River, PA 66 enters Armstrong County and begins a concurrency with Pennsylvania Route 56 in Apollo.

As PA 56/PA 66 enter the boro of North Apollo they parallel the Kiskiminetas River.

As PA 66 continues to parallel the Kiskiminetas River, it is called Lincoln Avenue.

In Rayburn Township, PA 28/PA 66 intersect the western terminus of Pennsylvania Route 85.

In South Bethlehem, PA 28/PA 66 become Broad Street and meet the northern terminus of Pennsylvania Route 839.

After crossing the Clarion River, PA 66 leaves I-80 at exit 60 (trumpet interchange).

At the mainline ones, a staffed full-service lane existed, accepting cash or credit cards.

On October 27, 2019, all-electronic tolling was implemented along the Amos K. Hutchinson Bypass section of PA 66.

The Amos K. Hutchinson Bypass uses all-electronic tolling, with tolls payable by toll-by-plate (which uses automatic license plate recognition to take a photo of the vehicle's license plate and mail a bill to the vehicle owner) or E-ZPass.

As of 2024[update], the mainline toll barrier between exits 4 and 6 costs passenger vehicles $5.50 using toll-by-plate and $2.90 using E-ZPass.

is an 8-mile-long (13 km) business route in Westmoreland County, Pennsylvania, connected two fingers of suburbia located east of Pittsburgh.

[12] The route begins nearly a mile south of the original terminus of PA 66, at a juncture with US 30 (which loops as a freeway around the city).

It is cosigned with US 119 and PA 819 to the city center, before traveling on its own accord through several suburbanized miles.

[12] The route then becomes more rural, as it provides a free connection to the east-central edge of suburban Pittsburgh at Delmont.