NY 22B begins at NY 22 in Peru, just north of a bridge over the Little Ausable River. It briefly runs west until it reaches the grounds of the Peru Central School District building, and makes a sharp curve to the north at the intersection of Clinton County Route 37, replacing the trajectory of Clinton CR 39. It continues north through farmland on the west side and forestland on the east side but briefly curves northeast and runs over a small bridge over Arnold Brook. North of that waterway farmland begins to run along both sides of the road, before the intersection with Broad Hollow Road, where it then makes another curve to the northwest before the intersection with Fox Farm Road. Along the way it turns north again as it passes a local Veterans of Foreign Wars post, then after the intersects a local road named Blake Road curves back to the northwest before the intersection with Mason Avenue just before entering the former village of Schuyler Falls. From that point it intersects the northern terminus of Clinton County Road 40 then crosses a bridge over the Salmon River while curving from northwest to north-northwest before a brief overlap with Clinton County Road 33 between Norrisville Road and Salmon River Road. North of the community, the route runs through more local farmland and at one point intersects the western terminus of Clinton County Road 32, a road known as Irish Settlement Road, which leads to NY 22 at Exit 36 on the Adirondack Northway and the western edge of the Plattsburgh International Airport. At the intersection with Broadwell Road, NY 22 enters the western edge of Morrisonville, where it turns northeast and after the intersection with Clinton County Road 31, and enters the community entirely as it runs along the southern banks of the Saranac River, shortly before crossing a bridge over that river just west of the intersection with Clinton County Road 16. From there the road runs along the north bank of the Saranac, which almost meets the road again at the bridge over Mead Brook, then river turns away to the southeast. NY 22B continues to run relatively east as it passes the north side of the Clinton County Airport, and finally terminates at NY 3, which continues east towards the City of Plattsburgh.
