The South Esk springs from the eastern foothills of the Ben Lomond plateau near Mathinna and the river's course describes an arc around the entire southern promontory of the mountain – running through Fingal, Avoca and Evandale before winding its way northwest through Perth, Longford and Hadspen.

The river is subject to flooding which overflows at Lake Trevallyn to create the spectacle of high rapids coursing through the narrows of the Gorge.

[6] The Panninher, Tyrernotepanner and Leterremairrener clans of the North Midlands Nation occupied the territories to the west of the river.

The Aboriginal clans exploited the hunting grounds alongside the river and took the native freshwater mussel for food.

The ethnographic record describes particular meeting areas, or 'resorts', on the river; such as Stony Creek, near Llewellyn; Glen Esk (near Nile); Native Point, near Perth; and at Hadspen.