The river leaves the Shield near the Alberta border and enters the Interior Plains where it becomes meandering, with numerous sand bars and small islands.

Instead, its morphology may be the result of catastrophic paleoflooding that originated from Glacial Lake Agassiz during late Pleistocene time and flowed through the Clearwater and Athabasca river valleys on its way to the Arctic Ocean.

[10] Rock-paintings along the upper portion of the river, shapes and symbols on rock surfaces, suggest that the area was already inhabited 5,000 years ago.

[5] During European exploration and the fur trade of the 18th century, the lower Clearwater River was part of an important canoe route between Hudson Bay and Montreal in the east, and the District of Athabasca in the west.

The rough Precambrian upper portion of the Clearwater River was a barrier to the traders until 1778, when explorer Peter Pond crossed the Methye Portage to bypass it.

Methye Portage extended between Lac La Loche and the Clearwater River, forming a 19-kilometre (12 mi) overland link on the route from Churchill, Manitoba to Athabasca, Alberta.