The headwaters of the river are in the Whicher Range below Chapman Hill and flows in a northerly direction through the City of Busselton until discharging into the Vasse Estuary and then the Indian Ocean via Wonnerup Inlet and Geographe Bay.
The river is named after French seaman Thomas (Timothy) Vasse, who disappeared in the area June 1801 during Nicolas Baudin's expedition.
It is estimated that 81.5% of the Vasse River catchment has been cleared.