Evaluation and analysis of water quality variations were performed with integrated consideration of water quality parameters, hydrological-meteorologic and anthropogenic factors in Cao-E River, Zhejiang Province of China. Cao-E River system has been polluted and the water quality of some reaches are inferior to Grade V according to National Surface Water Quality Standard of China (GB2002). However, mainly polluted indices of each tributary and mainstream are different. Total nitrogen (TN) and total phosphorus (TP) in the water are the main polluted indices for mainstream that varies from 1.52 to 45.85 mg/L and 0.02 to 4.02 mg/L, respectively. TN is the main polluted indices for Sub-watershed I, II, IV and V (0.76 to 18.27 mg/L). BOD5 (0.36 to 289.5 mg/L), CODMn (0.47 to 78.86 mg/L), TN (0.74 to 31.09 mg/L) and TP (0 to 3.75 mg/L) are the main polluted indices for Sub-watershed III. There are tow pollution types along the river including nonpoint source pollution and point source pollution types. Remarkably temporal variations with a few spatial variations occur in nonpoint pollution type reaches (including mainstream, Sub-watershed I and II) that mainly drained by arable field and/or dispersive rural dwelling district, and the maximum pollutant concentration appears in flooding seasons. It implied that the runoff increases the pollutant concentration of the water in the nonpoint pollution type reaches. On the other hand, remarkably spatial variations occur in the point pollution type reaches (include Sub-watershed III, IV and V) and the maximum pollutant concentration appears in urban reaches. The runoff always decreases the pollutant concentration of the river water in the seriously polluted reaches that drained by industrial point sewage. But for the point pollution reaches resulted from centralized town domestic sewage pipeline and from frequent shipping and digging sands, rainfall always increased the concentration of pollutant (TN) in the river water too. Pollution controls were respectively suggested for these tow types according to different pollution causes.