The Latrobe River and its associated sub-catchment is an important source for the Gippsland Lakes, draining the south eastern slopes of the Great Dividing Range.

The Latrobe River rises below Dick Hill, from the southern slopes of the Baw Baw plateau, part of the Great Dividing Range, between Powelltown and Noojee where it shares a watershed with the Little Yarra River, in a state forestry area.

The river flows generally in an easterly direction, then south, and then east again through the Latrobe Valley, joined by seventeen tributaries including the Ada, Toorongo, Loch, Tanjil, Morwell, Tyers, and Thomson rivers, before reaching its mouth in Lake Wellington east of Sale where it forms its confluence with the Avon.

[5] The Latrobe River flows through Lake Narracan, a storage reservoir near Newborough built to supply cooling water for the nearby brown coal fired power stations, and through Lake Victoria before emptying into the Bass Strait.

[8] According to Les Blake, in 1841 William Adams Brodribb, an early settler,[10] named the river in honour of Charles La Trobe, Lieutenant Governor of the Port Phillip District.