Coastal aquaculture is faced with extreme variation in water quality. The Deeba Triangle on Lake Manzala is the largest marine coastal aquaculture-producing area on the Egyptian Mediterranean. Samples from 16 ponds were taken during four seasons (2014–2015), to investigate the variation of 12 water quality parameters at that region. We tested the hypothesis that there is no spatial or temporal variation in water quality of the fish ponds. Fish ponds were statistically clustered into three groups (p = 0.0005) coincident with their geographical location. Hypersaline and transparent waters characterized the western ponds; higher dissolved oxygen and higher nutrients characterized the central region. These spatial differences were principally due to variations in salinity and nutrients of the water sources used for irrigation of the ponds and to differences in the aeration management styles. Strong seasonality was seen in water temperature (following air temperature), nutrients, and turbidity (following the seasonal cycles of various water sources from the Lake Manzala and the seasonality of the petrochemical plants effluents close to these ponds). We conclude that municipal effluents significantly affected, spatially and temporally, the quality of the irrigation water used for coastal aquaculture purposes, which consequently might affect fish yield.