The eastern terminus was moved to its current location at US 222 (now PA 272) in the 1930s, with US 222 replacing the route east of there.

From PA 283, the route passes a couple businesses before heading into agricultural areas, turning to the east.

The road crosses Norfolk Southern's Lititz Secondary railroad line at-grade and enters the borough of East Petersburg, where the name becomes State Street.

PA 722 heads northeast through residential areas with some businesses, curving to the east and intersecting Lemon Street.

The route heads through Groffs Corner and passes to the south of a farm before turning southeast past more homes and reaching a junction with PA 501 in Neffsville.

[5] PA 722 was designated by 1930 to run from US 230 (Harrisburg Pike) in Bamford east to US 222 and the eastern terminus of PA 772 in Brownstown, heading north on State Road, east on its current alignment to Oregon, and northeast on Oregon Pike.