The route begins in Oxford and passes through rural areas of western Chester County, serving Cochranville, Parkesburg, Compass, and Honey Brook.

The route fully enters Lower Oxford Township and becomes Limestone Road, passing northeast through a mix of farms and homes before reaching a partial cloverleaf interchange with the US 1 freeway.

The route runs north through more farmland before it reaches the community of Cochranville, where it turns northeast past homes and businesses and intersects PA 41.

At this point, the road becomes North Church Street and passes under Amtrak's Keystone Corridor railroad line before it runs through woodland with some residential development.

PA 10 leaves Parkesburg for Sadsbury Township and becomes Octorara Trail, running northwest through farmland with some homes.

[2][3] The road enters Honey Brook Township and heads into agricultural areas with some trees and residences containing several Amish farms.

Past this intersection, the route becomes Conestoga Avenue and passes more homes before heading back into Honey Brook Township on Twin County Road.

PA 10 runs north-northwest through farmland with some homes, crossing the West Branch Brandywine Creek before heading northeast and ascending a small forested hill named Welsh Mountain.

[2][3] PA 10 enters Caernarvon Township in Lancaster County and descends the hill into farmland, continuing to the north and crossing the Conestoga River.

[2][5] The road crosses into Caernarvon Township in Berks County and intersects SR 2089, a four-lane freeway that provides access to northbound I-176.

PA 10 fully enters Robeson Township and runs through wooded areas with some development prior to turning north and passing farm fields as it reaches the community of Plowville.

The route curves north again and passes near commercial development as it enters Cumru Township and comes to ramps providing access to and from the southbound direction of I-176.

The route continues north through woodland with some homes and commercial development to the west of the Schuylkill River before it enters the city of Reading.

The route continues west between neighborhoods and businesses to the south and the Schuylkill River Trail and the US 422 freeway to the north before it comes to its northern terminus at an intersection with US 222 Bus.

[14][15] The route was realigned to a new alignment south of the US 30 intersection north of Parkesburg in the 1950s, having previously followed current Hershey Lane and a concurrency with US 30.