The Moorabool River drains a 2170 km² area located roughly between Ballarat, Geelong, Little River, and Ballan.
It rises as two streams, the East Moorabool and West Moorabool Rivers, in the high ground on the southern side of the Great Dividing Range near Gordon (between Ballarat and Ballan). The landscape in the headwaters area is hilly and rolling with a mixture of eroded sedimentary and high-fertility volcanic soils. Rainfall can be as high as 1000 mm. Most of the land is cleared for grazing and broad acre cropping, but there are substantial areas used for intensive irrigated agriculture, in particular potato growing.
Both of the upper branches have had significant water storages constructed: the largest is the Lal Lal Reservoir on the East Moorabool. Despite the extensive areas of cleared land it flows through, the Moorabool branches are generally clear-flowing with good water quality. The West Moorabool, however, is heavily infested with willows and has unstable banks. While to Moorabool as a whole is classified as being in moderate condition, the West Moorabool is rated as poor condition.
In the middle reaches, the two Moorabool Rivers flow through mostly sedimentary country, with some granite-derived soils. Rainfall averages around 600-700 mm and several substatial areas of native forest remain intact. The two streams meet west of Elaine. This section, from the confluence south to about Sheoaks (15 kilometres south-east of Meredith), retains significant biodiversity values and, unlike the remainder of the river, is rated by the Department of Primary Industries as being in good condition.
Further downstream, the Moorabool passes through generally flat terrain with rainfall in the 500 to 600 mm range. It flows roughly parallel to the Ballarat-Geelong road, heading south and a little east, passing east of Leithbridge and Bannockburn and through Batesford before joining the Barwon River at Fyansford, an outer suburb of Geelong.
Salinity increases downstream of the confluence, exceeding 1,000EC at times, and nutrient loads become excessive during low-flow periods. Heavy flow diversions in the high-rainfall upstream part of the catchment, mainly for urban water supply, make the Moorabool one of the more severly flow-stressed rivers in the southwest. For continued health, particularly during the summer months, it depends on releases from the Lal Lal and Bostock Reservoirs.
To the west, the Moorabool Catchment adjoins the Leigh River Catchment. To the east, it is divided from the Little River by the Brisbane Ranges, while the headwaters of the East Moorabool are close to those of the Werribee River.