The objective of this study was to identify the spatial and temporal variabilities of selected nutrients in the Setiu Wetlands Lagoon (SWL), Malaysia. Water samples were collected quarterly at ten monitoring sites. This study presents results from a 10-year field investigation (2003 to 2010 and 2014 to 2015) of water quality in the SWL. For the spatial pattern, four clusters were identified with hierarchical cluster analysis. Analysis of the temporal trend shows that the high total suspended solid loading in 2010 was due to large-scale land clearing upstream of the SWL. The enrichment of ammonium after 2010 could plausibly be due to land-based aquaculture diffuse discharges. In 2005-2007, expansion of oil palm plantations within the Setiu catchment had doubled the phosphorus concentration in the SWL. The natural and anthropogenic alterations of the lagoon inlets profoundly influenced the spatial distribution patterns of nutrients in the SWL. These results suggest that intense anthropogenic disturbances close to the SWL accounted for the water quality deterioration.