A novel fouling-resistant nanofiltration mixed-matrix membrane was obtained by the incorporation of 2D boron nitride nanosheets (BNNS) in polyethersulfone (PES). The addition of just 0.05 wt% of BNNS into the PES matrix led to a 4-fold increase in pure water permeance with a 10% decrease in the rejection of the dye Rose Bengal; up to 95% rejection of humic acid and nearly 100% flux recovery over two cycles in cross-flow fouling tests without the need for chemical cleansing. This performance is attributed to the uniform distribution of the BNNS in the PES matrix, observed via Raman mapping, and the surface chemistry and structure of the BNNS, which hydrophilised the polymer matrix and reduced its surface roughness. The low amount of BNNS filler needed to render the mixed-matrix membrane fouling-resistant opens the way to its use in waste-water treatment applications where organic fouling remains a major challenge.