PA 33 begins at a trumpet interchange with I-78 in Lower Saucon Township in Northampton County, which is in the Lehigh Valley.
From this interchange, the route heads northwest as a four-lane freeway and heads onto the Gene Hartzell Memorial Bridge, passing over Norfolk Southern's Lehigh Line and the Lehigh River, where the highway briefly cuts through the southwestern tip of the city of Easton before crossing the Lehigh Canal into Bethlehem Township.
Past the bridge, the freeway passes farm fields before it comes to a partial cloverleaf interchange with Freemansburg Avenue in a business area adjacent to St. Luke's Hospital-Anderson Campus.
Following this, PA 33 curves north near commercial development and reaches a diamond interchange with William Penn Highway, with a park and ride lot located at the northwest quadrant of this interchange.
The route heads near a mix of residential development and farmland, curving northeast before turning north and coming to a cloverleaf interchange with the US 22 freeway.
After the US 22 interchange, the freeway crosses into Lower Nazareth Township and reaches a partial cloverleaf interchange with Hecktown Road.
PA 33 continues north past farm fields and curves northeast as it comes to a partial cloverleaf interchange with PA 248 in a business area.

Past this interchange, the route enters Palmer Township and runs through a mix of farm fields and industrial development, coming to a diamond interchange with Main Street that serves the borough of Tatamy to the east.
The freeway curves north and crosses Bushkill Creek into the borough of Stockertown, where it passes over Norfolk Southern's Cement Secondary line and a railroad spur and turns northwest to reach a diamond interchange with PA 191.
PA 33 continues past industrial areas and leaves Stockertown for Plainfield Township, passing over a Norfolk Southern railroad spur.
The route heads into wooded areas and crosses into Bushkill Township, where it reaches a diamond interchange with Henry Road that serves the community of Belfast to the east.
A park and ride lot is located within the southeast quadrant of this interchange.
Past this interchange, the freeway heads east of the Jacobsburg Environmental Education Center as it continues through woodland with some farm fields and residential development.
PA 33 turns north and crosses back into Plainfield Township, where it comes to a partial cloverleaf interchange with PA 512 in an area of businesses that serves the borough of Wind Gap.
Past this interchange, the freeway passes through a corner of Wind Gap before it continues back into Plainfield Township and heads into forested areas, heading through a gap in the Blue Mountain ridge.
The route turns northeast and comes to a southbound exit and northbound entrance with Broadway that provides access Wind Gap.
At this interchange, the freeway passes over the Appalachian Trail.

At the interchange with Broadway, PA 33 crosses into Hamilton Township in Monroe County, which is in the Pocono Mountains region of the state, and continues through forested areas, turning northwest and entering Ross Township.
The freeway curves north and then northeast, crossing back into Hamilton Township and turning northwest.
The route reaches the community of Saylorsburg, where a southbound exit and entrance connects to Wilkes Barre Turnpike and a northbound exit and entrance connects to Cherry Valley Road.
From here, PA 33 turns northeast and runs through wooded areas with some fields and homes, soon making a curve to the north.
The freeway comes to a trumpet interchange with US 209, at which point US 209 joins PA 33 in a concurrency on the freeway.
The two routes continue north-northeast through woodland with some development, coming to a diamond interchange with Manor Drive that serves the community of Snydersville.
From here, the freeway passes west of Monroe County Correctional Facility before PA 33 exits from the US 209 freeway at a northbound exit and southbound entrance, with signs leading travelers to eastbound and from westbound I-80 via US 209.
After this,
PA 33 begins at a trumpet interchange with I-78 in Lower Saucon Township in Northampton County, which is in the Lehigh Valley. From this interchange, the route heads northwest as a four-lane freeway and heads onto the Gene Hartzell Memorial Bridge, passing over Norfolk Southern's Lehigh Line and the Lehigh River, where the highway briefly cuts through the southwestern tip of the city of Easton before crossing the Lehigh Canal into Bethlehem Township. Past the bridge, the freeway passes farm fields before it comes to a partial cloverleaf interchange with Freemansburg Avenue in a business area adjacent to St. Luke's Hospital-Anderson Campus. Following this, PA 33 curves north near commercial development and reaches a diamond interchange with William Penn Highway, with a park and ride lot located at the northwest quadrant of this interchange. The route heads near a mix of residential development and farmland, curving northeast before turning north and coming to a cloverleaf interchange with the US 22 freeway. After the US 22 interchange, the freeway crosses into Lower Nazareth Township and reaches a partial cloverleaf interchange with Hecktown Road. PA 33 continues north past farm fields and curves northeast as it comes to a partial cloverleaf interchange with PA 248 in a business area.
Past this interchange, the route enters Palmer Township and runs through a mix of farm fields and industrial development, coming to a diamond interchange with Main Street that serves the borough of Tatamy to the east. The freeway curves north and crosses Bushkill Creek into the borough of Stockertown, where it passes over Norfolk Southern's Cement Secondary line and a railroad spur and turns northwest to reach a diamond interchange with PA 191. PA 33 continues past industrial areas and leaves Stockertown for Plainfield Township, passing over a Norfolk Southern railroad spur. The route heads into wooded areas and crosses into Bushkill Township, where it reaches a diamond interchange with Henry Road that serves the community of Belfast to the east. A park and ride lot is located within the southeast quadrant of this interchange. Past this interchange, the freeway heads east of the Jacobsburg Environmental Education Center as it continues through woodland with some farm fields and residential development. PA 33 turns north and crosses back into Plainfield Township, where it comes to a partial cloverleaf interchange with PA 512 in an area of businesses that serves the borough of Wind Gap. Past this interchange, the freeway passes through a corner of Wind Gap before it continues back into Plainfield Township and heads into forested areas, heading through a gap in the Blue Mountain ridge. The route turns northeast and comes to a southbound exit and northbound entrance with Broadway that provides access Wind Gap. At this interchange, the freeway passes over the Appalachian Trail.
At the interchange with Broadway, PA 33 crosses into Hamilton Township in Monroe County, which is in the Pocono Mountains region of the state, and continues through forested areas, turning northwest and entering Ross Township. The freeway curves north and then northeast, crossing back into Hamilton Township and turning northwest. The route reaches the community of Saylorsburg, where a southbound exit and entrance connects to Wilkes Barre Turnpike and a northbound exit and entrance connects to Cherry Valley Road. From here, PA 33 turns northeast and runs through wooded areas with some fields and homes, soon making a curve to the north. The freeway comes to a trumpet interchange with US 209, at which point US 209 joins PA 33 in a concurrency on the freeway. The two routes continue north-northeast through woodland with some development, coming to a diamond interchange with Manor Drive that serves the community of Snydersville. From here, the freeway passes west of Monroe County Correctional Facility before PA 33 exits from the US 209 freeway at a northbound exit and southbound entrance, with signs leading travelers to eastbound and from westbound I-80 via US 209. After this, 
Pennsylvania Route 33