The operationalization of water resource protection initiatives for surface water resource quality and equitable water quality allocation is critical for sustainable socio-economic development. This paper assessed Blesbokspruit River Catchment’s water quality status, using the South African Water Quality standards and Water Quality Index (WQI). Protection levels for quality, and waste discharge for point sources were set and evaluated using the total maximum daily loads (TMDLs) and chemical mass balance (CMB) techniques, respectively. The study found that the water quality results for the analysed physico-chemical parameters (Na+, Ca2+, Mg2+, Cl−, F−, pH, EC, SO42−) of the data collected from 2015 to 2022 were within the limits of the water quality standards, except for NO3− and PO42−. The water quality from the study area was categorized as acceptable for drinking purposes with the WQI of 54.80. The application of the TMDL approach resulted in the 77.96 mS/m for electrical conductivity (EC), 9.92 mg/L for phosphate (PO42−), and 15.16 mg/L for nitrate NO3− being set as the protection levels for the catchment. The CMB was found to be a useful tool for the evaluation of point source discharges into water resources. The study recommends the application of TMDL and CMB techniques in water resource protection practice.