It is formed at Johnstown in southwestern Cambria County by the confluence of the Little Conemaugh and Stoneycreek rivers. It flows generally WNW, in a winding course through the mountains along the northern edge of Laurel Hill and Chestnut Ridge. Northwest of Blairsville it is joined by Blacklick Creek. At Saltsburg it is joined from the south by the Loyalhanna River to form the Kisminetas. Along much of its lower course it forms part of the border between Westmoreland and Indiana counties.
The Kiskiminetas-Conemaugh river basin flows through a scenic mountainous country that forms the heart of the historic coal-producing areas of western Pennsylvania. The watershed is considered among the most degraded in the state, largely from abandoned mine drainages. The recovery of the river has been an important ongoing ecological managemnt project of state and private agencies.
The main branch rises in eastern Cambria County, along the western slope of the Appalachian ridge separating the watersheds of the Ohio and Susquehanna rivers.
From 1834 to 1854 the river was paralled by the Allegheny Portage Railroad, connecting the two branches of Pennsylvania Main Line Canal, with the western terminus of the portage railroad at Johnstown.
The river flows through scenic mountainous areas but is considered severely degraded by abandoned mine drainages from the long exploitation of the region's coal resources.
The Kiskiminetas-Conemaugh river basin flows through a scenic mountainous country that forms the heart of the historic coal-producing areas of western Pennsylvania.