A wide variety of organic micropollutants in drinking water pose a serious threat to human health. This study was aimed to reveal the characteristics of organic micropollution profiles in water from a drinking water treatment plant (DWTP) in the Yangtze River Delta, China and investigate the mutagenicity, health risk and disease burden through mixed exposure to micropollutants in water. The presence of organic micropollutants in seven categories in organic extracts (OEs) of water from the DWTP was determined, and Ames test was conducted to test the mutagenic effect of OEs. Meanwhile, health risk of exposure to organic micropollutants in finished water through three exposure routes (ingestion, dermal absorption and inhalation) was assessed with the method proposed by U.S. EPA, and disability-adjusted life years (DALYs) were combined to estimate the disease burden of cancer based on the carcinogenic risk (CR) assessment. The results showed that 28 organic micropollutants were detected in the raw and finished water at total concentrations of 967.28 ng/L and 1073.45 ng/L, respectively, of which phthalate esters (PAEs) were the dominant category (95.79% in the raw water and 96.61% in the finished water). Although the results of the Ames test for OEs were negative and the non-carcinogenic hazard index of the organic micropollutants in the finished water was less than 1 in all age groups, the total CR was 2.17 × 10−5, higher than the negligible risk level (1.00 × 10−6). The total DALYs caused by the organic micropollutants in the finished water was 2945.59 person-years, and the average individual DALYs was 2.21 × 10−6 per person-year (ppy), which was 2.21 times the reference risk level (1.00 × 10−6 ppy) defined by the WHO. Exposure to nitrosamines (NAms) was the major contributor to the total CR (92.06%) and average individual DALYs (94.58%). This study demonstrated that despite the negative result of the mutagenicity test with TA98 and TA100 strains, the health risk of exposure to organic micropollutants in drinking water should not be neglected.