The river gives the name to the Kakisa Formation, a stratigraphical unit of the Western Canadian Sedimentary Basin.

The Kakisa River originates in northern Alberta, immediately south of the Northwest Territories border, from Creighton Lake, at an elevation of 570 meters (1,870 ft).

3 kilometers (1.9 mi) east of the British Columbia border it turns north and flows back in the Northwest Territories.

It flows out at the eastern side of the lake, drops through the Lady Evelyn Falls before it is crossed by the Mackenzie Highway.

It continues northwards, then empties into the Mackenzie River, 30 kilometers (19 mi) downstream from the Great Slave Lake, at an elevation of 160 meters (520 ft).