The Songhua River Basin (SRB) is located in the northern part of Northeast China, and includes the Inner Mongolia Autonomous Region, Jilin Province, and Heilongjiang Province. The SRB is also known as the Northeast Old Industrial Base and has a reputation for industrial production, which had some negative impacts on the aquatic environment of the Songhua River. Research on the levels and patterns of the aquatic contamination risk posed by the riverside enterprises in the SRB are valuable for controlling water contamination risk and optimizing the riverside industrial layout. Thus, it is essential to investigate the industrial enterprises generating wastewater in the basin and to estimate their risk of contaminating the aquatic environment. Based on theList of National Key Monitored Enterprises Generating Wastewater in 2012, we identified 45 key enterprises distributed within 1 km of the river banks, as potential sources of contamination. We assessed the risk level of these sources by calculating the annual volume of wastewater generated by the enterprises and estimated the buffering capacity of the local waters by analyzing the background water quality. We also evaluated the sensitivity of the social-economic-natural complex ecosystem to potential water contamination by investigating the total population of the districts, the secondary industrial outputs of the districts, and the distribution ranges of rare and endangered species. The results showed that Mudanjiang City (with the middle reaches of the Mudan River) suffered the most serious contamination risk because of the large volume of wastewater generated annually, the low buffering capacity of the local waters, and the high sensitivity of the natural ecosystem to potential water contamination. Changchun City (with part of the reaches of the Yinma and Yitong Rivers), Yichun City (with all reaches of the Tangwang River) and Dunhua City (with all reaches of the Hailang River, and part of the reaches of the Mudan River) showed the low buffering capacity and the high sensitivity, and thus risk prevention should be strengthened in these districts. In addition, owing to the large volume of wastewater generated annually, Jilin City (with part of the reaches of the West-flowing Songhua River) and Qitaihe City (with part of the reaches of the Woken River), particularly the former with the higher sensitivity of its social and economic ecosystems, should improve the capacity of risk management to reduce the possibility of water contamination in these districts. This study analyzed the levels and patterns of potential water contamination risk, and revealed the causes of spatial differences in the risk of aquatic environment contamination among riverside areas in the SRB. Moreover, it provided a reference for development of riverside industrial zones, prevention and emergency response to sudden water pollution accidents, and long-term risk management of water pollution. In the short term, the key riverside enterprises should improve the efficiency of their wastewater treatment and effectively control the risk of pollution. In the long term, it is important to accelerate the adjustment of the industrial layout and to improve legislation for pollution prevention and control.