From source to mouth, the river is joined by nineteen minor tributaries; and descends 567 metres (1,860 ft) over its 392-kilometre (244 mi) course.

[5] The river rises below Musk near Trentham and Lyonville from where it heads northward to Glenlyon and on to Loddon Falls.

After Newstead the river flows into the Cairn Curran Reservoir (147,000 ML[citation needed]), before emerging at Baringhup and continuing north to Eddington.

[7] Approximately 10 kilometres (6.2 mi) south of Kerang water flows are increased due to water entering from the Macorna Channel, and the higher flows are maintained for the next 15 kilometres (9.3 mi) of river up to the Kerang Weir.

In the Djadjawurrung and the Barababaraba languages, the name for the river is Gunbungwerro, with werro and wurru meaning "lips" or "mouth".

In the Gannawarra and Barababaraba languages, the name for the river is Mudyin gadjin, meaning "[he] picked up water".

[2][3][9] When reasonable water levels flow, the Mill Rapid downstream of the Calder Hwy bridge provides technical whitewater kayaking of Grade 3 standard featuring a short fast run.

Upstream of the Calder Hwy bridge kayakers and canoeists will have a pleasant paddling experience but may have to share the river with swimmers, fishers, and waterskiers.

The main fish species in the river's lower reaches are redfin, golden perch and Murray cod.