PA 41 runs northwest-southeast along a two-lane undivided road called Gap Newport Pike, passing through mostly rural areas of Chester and Lancaster counties and serving Avondale, Chatham, Cochranville, and Atglen.

From the state line, the route heads northwest on two-lane undivided Gap Newport Pike, passing through farmland with some development.

Then route heads into the borough of Avondale, where it crosses an East Penn Railroad line at-grade and comes to an intersection with Baltimore Pike.

Here, the road becomes Pennsylvania Avenue and crosses the East Branch White Clay Creek, running through wooded residential areas.

The route briefly passes through a corner of West Sadsbury Township before it enters the borough of Atglen and comes to an intersection with PA 372.

The road curves northwest and crosses back into West Sadsbury Township, passing through a mix of farm fields and development.

[2][4] At this point, the route enters the Pennsylvania Dutch Country of eastern Lancaster County, which is home to many Amish farms.

[5][6] The roadway heads west past homes and businesses as it bypasses the borough of Christiana to the north, briefly gaining a center left-turn lane.

The route heads north and crosses into Salisbury Township, where it enters the residential community of Gap and has a junction with Strasburg Road before it gains a second southbound travel lane.

PA 41 heads into business areas and comes to its northern terminus at a junction with US 30 (Lincoln Highway), which provides access to the city of Lancaster to the west.

[2][4] PA 41 serves as part of the main route connecting Wilmington to Lancaster and sees heavy truck traffic.

In 1993, the Pennsylvania Department of Transportation (PennDOT) began the process of planning improvements to the road to enhance safety and the movement of freight.

The widening and bypass plans drew the opposition of Governor Ed Rendell and an activist group called Safety Agricultures Village and Environment in 2003, both of whom instead supported a truck ban and traffic-calming measures such as roundabouts along the road.

[26] In 2003, PennDOT painted white dots in the travel lanes along portions of PA 41 prone to aggressive driving in order to reduce tailgating along with adding rumble strips.