In Woods Cree, the word aðapaskāw means "[where] there are plants one after another", likely a reference to the spotty vegetation along the river. The Canadian Heraldic Authority has named Athabaska Herald after the river.
Sekani, Shuswap, Kootenay, Salish, Stoney and Cree tribes hunted and fished along the river prior to the European colonization. David Thompson and Thomas the Iroquois travelled through the Athabasca Pass in 1811. In 1862, the Atahbasca springs area was crossed during the Cariboo Goldrush.
Athabasca River originates at the toe of the Columbia Glacier, between Mount Columbia, Snow Dome and the Sir Winston Churchill Range, in Jasper National Park, at an altitude of approximately .
The river flows along icefields, through gorges, offers wildlife habitat on its shores and adjacent marshes. National and provincial parks were established to protect this habitats and landscapes, such as Jasper National Park, Sundance Provincial Park, Carson-Pegasus Provincial Park, Obed Lake Provincial Park, William A. Switzer Provincial Park. The river also crosses the southeast limits of Wood Buffalo National Park, where its course is marked by rapids, impeding navigation north of Fort McMurray.
The Athabasca River travels before draining into the Peace-Athabasca Delta near Lake Athabasca, south of Fort Chipewyan and Wood Buffalo National Park. From there, its waters flow north as Slave River into the Great Slave Lake, which discharges through the Mackenzie River system into the Arctic Ocean. The cumulative drainage area is .
Many communities are located on the banks of this river. Among the larger ones are Jasper, Hinton, Whitecourt, Athabasca and Fort McMurray.