As of March 2016, PA 33 north of the US 22 interchange in Bethlehem Township was the busiest state highway or street in the Lehigh Valley with an average of 68,800 vehicles daily.

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.

[4][5] 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 Tatamy and the warehouse district to the east.

The freeway curves north and crosses Bushkill Creek into 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 serving Belfast to the east.

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.

The two routes continue northeast through woodland with some development, crossing McMichael Creek and coming to a diamond interchange with Manor Drive that serves Snydersville.

From here, the freeway passes west of Monroe County Correctional Facility and crosses Appenzell Creek before PA 33 exits northbound from the US 209 expressway, with signs leading travelers to eastbound and from westbound I-80 via US 209.

[7] On March 21, 2009, a tractor-trailer carrying 32,000 pounds of hydrofluoric acid overturned on southbound PA 33 in Plainfield Township, prompting the evacuation of about 5,000 people.

[8] On January 31, 2013, ground was broken for a new interchange at Main Street in Palmer Township to the west of Tatamy, with Governor Tom Corbett in attendance.