[8] The upper reaches are contained in the rugged, heavily forested and largely inaccessible, Avon Wilderness Park.

The river then forms a boundary for the Macallister Irrigation District, with Nuntin Creek joining 10 kilometres (6.2 mi) downstream of Stratford contributing a large amount of irrigation drainage to the river.

Considerable demand is placed on the Latrobe and Thomson Rivers for supply of Melbourne's water, industrial use in Australia's largest pulp and paper mill and the power industry in the Latrobe Valley, and for irrigation.

The river was important to the indigenous Gunai/Kurnai people, highlighted by Knob Reserve, 3 kilometres (1.9 mi) south of Stratford, being part of the Gunai/Kurnai Bataluk Cultural Trail.

The trail highlights the places of cultural significance to the first inhabitants across East Gippsland.