This study aimed to determine mutagen contamination, to compare the differences between inlet and outlet distribution, and the possible impacts on public health. Water samples were collected from four different waterworks in Guangzhou, China. The Ames test was conducted to investigate the potential mutagenicity caused by organic extracts from drinking water sources and peripheral water. Organic content was extracted with XAD-2 resin column and organic solvents, and toxicity was tested in three doses of extract equivalent, 0.2, 0.4 and 0.8 L source water. The results of the Ames test showed that all the organic extracts from water samples could induce different levels of mutagenic potentials in the absence of S9 mix, which indicated mutagenicity and strain. Comparing with TA98, TA100 was more sensitive in genotoxicity. Mutagenic enhancement factors were found in both drinking water sources and peripheral water. Water treatment technologies with different disinfection ways could increase the mutagenicity of water, but the biological significance of mutagenicity of the organic extracts remained to be further confirmed. The results suggested that it was necessary to concern the relationship between source water, water treatment unit and the mutagenicity factors of water.