Abstract This investigation focused on the seasonal variation and spatial fate of chlorination disinfection by-products (CDBPs) in a drinking water distribution system located in a region where very significant seasonal variations in water temperature and surface water quality occur. The analysis of a large number of collected samples showed that the seasonal and geographical variations of both groups of CDBPs under study—trihalomethanes (THMs) and haloacetic acids (HAAs)—were particularly important in this region. THM levels in summer and fall were, on average, about five times higher than in winter, whereas average HAAs in spring were about four times higher than in winter. THMs increased and stabilized in the extremities of the distribution system, whereas HAAs begin to increase, and then decrease (mainly due to a reduction of dichloroacetic acid). This decrease was significantly higher in warm waters than in cold waters, which led to the hypothesis of microbial degradation of HAAs as water approaches the system extremities. In fact, regression models for the occurrence of both CDBPs showed that the residence time of water was one important parameter in explaining the fate of both CDBPs. The spatio-temporal portrait of both groups of CDBPs that was generated demonstrates that, due to their high intra-seasonal changes, the calculation of average annual levels of these substances for compliance with regulations can vary widely. The results used in the portrait of CDBP behavior are also relevant in terms of exposure assessment for future epidemiological studies on human reproductive outcomes in the region.