PA 416 begins at the Maryland border in Montgomery Township, heading northwest on two-lane undivided Mercersburg Road.

From the state line, the route heads through a mix of farms and woods with some homes, passing through the community of Nova.

The road passes a few residential and commercial areas before crossing into Peters Township and heading into agricultural surroundings.

[5] By 1930, the current alignment of the route between the Maryland border and PA 16 east of Mercersburg was an unnumbered, unpaved road.

[6] PA 416 was extended south from Mercersburg to the Maryland border southeast of Welsh Run in 1937, following its present alignment.