Conodoguinet Creek is a 104-mile-long (167 km) tributary of the Susquehanna River in south central Pennsylvania in the United States. Conodoguinet Creek joins the Susquehanna River upstream of Harrisburg. The water divide between Conodoguinet Creek and Conococheague Creek is sometimes used as the boundary between the Hagerstown Valley and the Cumberland Valley. It flows past many mills, including Maclay's Mill. The Appalachian Trail crosses the creek near Carlisle.