Flowing from east to west through Lake Gordon, the river continues west, passing through the Gordon Splits, a series of gorges once considered impassable until 1958 when Olegas Truchanas, a conservationist and nature photographer, was the first person to navigate the Gordon River in a kayak. The river flows north by west and then due north and finally due west as it reaches its mouth and empties into Macquarie Harbour at Wrights Bay.

From source to mouth, the river is joined by 25 tributaries including the Boyes, Holley, Serpentine, Orange, Denison, Sprent, Franklin, and the The river descends 570 metres (1,870 feet) over its 172-kilometre (107 mile) course; much of which is located in an uninhabited wilderness area, contained with the Franklin-Gordon Wild Rivers National Park and Southwest National Park. The lower part of the Gordon River is part of the Tasmanian Wilderness World Heritage Area and contains a cold-climate rainforest and rare trees. As with many rivers in western Tasmania, the water is fresh and drinkable, yet has the colour of weak tea due to the absorption of tannin from button grass growing in the catchment area.