The Wimmera River rises in the Great Dividing Range below Elmhurst, between Ararat and Avoca, and flows generally north and west, through Glenorchy, Horsham, Dimboola and Jeparit, also forming the eastern boundary of the Little Desert National Park.

It is joined by fourteen minor tributaries, including the Mackenzie River, before reaching its mouth at Lake Hindmarsh, near Jeparit.

Prior to the project's completion, up to 90 percent of water extracted from the Wimmera River was lost through evaporation and seepage.

The Wimmera-Mallee Pipeline system was expected to be many times more efficient[citation needed] and meant that there would be much less water extracted from the Wimmera River.

[citation needed] The Wimmera River at Horsham has been subject to periodic flooding, with peaks recorded as follows: In the Aboriginal Djadjawurrung and Jardwadjali languages the river is named Walla-walla, with no defined meaning; and Wamara, possibly meaning woomera or "throwing stick".