The Maligne River begins south of Maligne Lake. Forming from the meltwater of Replica Peak, the river heads north, passing under Mount Mary Vaux, Lysfran Peak, Mount Unwin, and Mount Charleton before emptying into Maligne Lake. The Maligne River drains the north end of Maligne Lake and heads northwest to Medicine Lake. It then flows west, entering the Athabasca River. Below Maligne Lake, it is a losing stream; its flow mostly disappears underground at Medicine Lake, only to reappear downstream in Maligne Canyon.