Pesticide use in rice farming is a common practice in the Mekong Delta and poses ecological risks to aquatic organisms, the environment, and human health. This study focused on the ecological risk assessment of pesticide use in rice farming using the PRIMET model as a decision support tool to evaluate the risks of pesticide exposure, ecotoxicity, and risk characterization, as well as employing the species sensitivity distribution (SSD) assessment model to calculate the potentially affected fraction (PAF) of species based on the computed predicted environmental concentrations (PECs) from PRIMET. The study involved collating and analyzing data on pesticide inventories and the application of 138 farmers, which formed the basis for pesticide use, farming practices,environmental variables, and ecological indicators from two provinces in the Mekong Delta: Dong Thap and Hau Giang. This study showed that pesticide use was high with a wide range of pesticide types. The ecotoxicity assessment indicated that some pesticides pose a potential acute and chronic risk to non-target organisms. The active ingredient identified as posing acute toxicity risk with an ETR >100 is the insecticide indoxacarb, which belongs to the chemical class of oxadiazine of which Arthropods were seen to be highly sensitive to when exposed making them more at risk even at very low concentrations. In contrast, fish generally exhibit moderate tolerance and are sensitive to certain chemicals. The risk characterization revealed that the ecological risks of pesticide use were higher in Dong Thap than in Hau Giang due to differences in ecological conditions, pesticide practices, and farming systems. Overall, this study highlights the need for improved pesticide management practices in rice farming in the Mekong Delta region to reduce ecological risks and protect the environment and human health. The practical and theoretical implications of this study are discussed.