Highway 65 travels from Highway 66 at a junction east of Matachewan, southeast to New Liskeard then northeast to the Quebec provincial border. The total length of Highway 65 is . With the exception of the community of Elk Lake, the section of the route between Highway 66 and Highway 11 passes through a remote and sparsely populated wilderness. The route becomes concurrent with Highway 11 and follows that route north for , bypassing the urban section of New Liskeard in the process.