The route is a two-lane road passing through rural areas, heading through the Pennsylvania Dutch Country in eastern Lancaster County that is home to several Amish families and rural areas in western Chester County, serving the communities of Bird-in-Hand, Intercourse, White Horse, Compass, and Wagontown.

Farther east, the route heads between industrial parks to the north and neighborhoods to the south before coming to a partial interchange with the US 30 freeway that does not have a ramp from westbound US 30 to PA 340.

Past this interchange, PA 340 runs through less dense areas of residential and commercial development with some farm fields.

[2][3] At this point, the route enters the Pennsylvania Dutch Country of eastern Lancaster County, which is home to many Amish farms and businesses catering to tourists.

The route crosses Mill Creek and continues east to the community of Bird-in-Hand, where it passes under Amtrak's Keystone Corridor railroad line.

The route heads into Salisbury Township and runs through more rural areas, passing through the community of Spring Garden.

Following this, the road runs east through more areas of farm fields, crossing Pequea Creek and passing through the community of Cains.

The route curves southeast before running east again and becoming the border between West Caln Township to the north and the city of Coatesville to the south.

The route passes through more wooded areas with some homes and fields, as well as Caln Meeting House, turning east onto Bondsville Road.

The route runs through wooded areas of residential development and comes to its eastern terminus at an intersection with US 30 Bus.

[13] PA 340 was assigned in 1928 to the alignment extending from US 222/PA 240 (Horseshoe Road) east of Lancaster to US 30/PA 1 in Gap via White Horse.

[15][16] By 1940, the western terminus was extended to US 22 (Herr Street) east of Harrisburg, following its current alignment (which replaced US 222) to US 30, which it ran concurrent with through Lancaster.