Based on water sample data collected from the Yangtze River Estuary (YRE) during four sampling periods in 2010 and 2011, the total nitrogen (TN) and total phosphorus (TP) content were evaluated using the traditional single-factor evaluation (TSE) and the fuzzy comprehensive evaluation (FCE). Statistical analyses showed that the average TN and TP for the four periods were 2.60 mg/L and 0.11 mg/L, respectively. August 2010 showed the lowest TN (1.57 mg/L), and February 2011 showed the highest TP (0.15 mg/L). The annual spatial distribution results indicated that an area of high TN concentration (TN ≥ 3.0 mg/L) occurred in the adjacent sea and increased on an eastward gradient. An area of high TP concentration (TP ≥0.10 mg/L) occurred in the inner YRE and decreased on an eastward gradient. There were significant differences in the results of TSE and FCE. The TSE results only reflected the TN evaluation results for certain locations of the YRE. The FCE method combined the effects of the TN and TP factors, and the results indicate that the Chinese water quality classification of Class 5 was dominant in the YRE.