The Kodungallur-Azhikode Estuary (KAE) is part of the Vembanad wetland ecosystem in south-west coast of India that has recently been designated as the Ramsar site. Modern aquaculture, agriculture and other human activities in the catchment area export huge amounts of organic and inorganic wastes into the KAE. In this perspective, influences of anthropogenic activities on water quality and phytoplankton production in the KAE were studied at multiple sites from July 2009 to June 2010. The linear correlation with salinity (r2=0.179, P<0.01), pH (r2=0.195, P<0.01,) and redox potential (Eh) (r2=0.188, P<0.01) was found to be significant with Chlorophyll-a (Chl-a) and negative correlation with turbidity (r2=-0.212, P<0.01, N=168), nitrate (r2=-0.297, P <0.01, N=168), and total dissolved solids (TDS) (r2=-0.266, P<0.01, N=168). The present study showed annual average gross primary productivity (gross PP) of 1580 ± 388 mgC m-3d-1 and net primary productivity (net PP) 790 ± 472 mgC m-3d-1, with significant monthly variation. The mean Chl-a content in the estuary also showed moderately high values (6.42 ± 3.91 mg m-3). In spatial scale, it varied from 5.07 ± 4.03 mg m-3 at Station II to 7.80 ± 6.07 mg m-3 at Station V. Primary productivity in the estuary was nitrogen limited during pre monsoon period, however average N: P ratio in the water column was well above the Redfield ratio during south west monsoon period (27.9 ± 14.2). Trophic Index (TRIX) analysis in the KAE also showed that estuary experiencing high productivity by the effect of eutrophication.