US 222 begins at an intersection with US 1 in the community of Conowingo in Cecil County, Maryland. (Following US 1 southwest to the Conowingo Dam across the Susquehanna River leads to the northern terminus of MD 222.) From this intersection, the route heads northwest on two-lane undivided Rock Springs Road, passing through a mix of fields and woods with some homes. The road curves to the north through woodland and passes east of the community of Oakwood. US 222 turns to the northeast and runs through fields and woods with some development, passing to the southeast of the Rock Springs Generation Facility in the community of Rock Springs before it comes to the Mason–Dixon line, which marks the border between the states of Maryland and Pennsylvania.