The Wilson Inlet catchment covers approximately 2,300 km². The Denmark and Hay Rivers are the two major rivers which flow into Wilson Inlet, they comprise 25% and 52% of the catchment areas respectively. The Denmark River, once saline, has been restored to a nearly fresh system, a rare example of reversing salinisation in similar catchments. Other tributaries include Scotsdale Brook, Sunny Glen Creek, Sleeman River, Cuppup Creek and Little River. Lake Saide wetlands and many smaller tributaries around the foreshore of the estuary are minor parts of the overall catchment.
The Wilson Inlet catchment is approximately 47% cleared of native vegetation and is predominantly occupied by livestock grazing (cattle and sheep), plantations, horticulture and residential land-uses. The area of the Wilson inlet itself is approximately 48 km².
There have been considerable modifications to the drainage of the catchment. Both the Denmark and Quickup rivers are dammed for potable water supply and there are many private farm dams throughout the catchment. Artificial drainage is present throughout agricultural areas of the catchment. Portions of Cuppup Creek and Sleeman River have been artificially modified to improve localised drainage.
Previous catchment nutrient loss modelling (Ecotones and Associates 2008) found that the Denmark River, Hay River and Cuppup Creek delivered the largest loads of nutrients to the inlet. Cleared agricultural catchments in high rainfall areas (Little River, Lower Denmark, Scotsdale, Sunny Glen Creek, Sleeman and Cuppup) were found to have a high nutrient loss intensity, particularly for phosphorus. Animal grazing land uses were identified as the largest source of nutrients.