Background: One of the most common diseases in free-range ducks in the Mekong Delta is botulism. Botulism is a poultry disease caused by botulinum exotoxin of Clostridium botulinum. Aim: To evaluate the prevalence of botulism in free-range ducks in the Mekong Delta and the risk of infection by determining the presence of C. botulinum in the farming environment. Methods: Research was carried out on 200 duck flocks with 187,050 individuals raised freely in the fields in the provinces of the Mekong Delta, including An Giang, Can Tho, Hau Giang, and Kien Giang. The ducks were diagnosed with botulism based on clinical symptoms. To demonstrate the presence of botulinum neurotoxins and identify serotype, samples of serum and/or gut were analyzed by mouse bioassay. Samples of soil (n = 600), water (n = 600), crabs (n = 216), and snails (n = 400) were taken from the grazing regions for C. botulinum analysis by PCR assay. Results: There were 1.19% (2,235/187,050) free-range ducks in the Mekong Delta positive for botulism. Clinical symptoms of botulism including limberneck, drooping eyelids–enlarged pupils, and leg paralysis were prevalent across free-range ducks, with the frequency of 87.92% (1,965/2,235), 90.07% (2,013/2,235), and 79.78% (1,783/2,235), respectively. The lesions of pulmonary edema–hemorrhage, hemorrhagic liver, and gas-producing intestines were common, accounting for 86.19% (362/420), 95.48% (401/420), and 92.14% (387/420), respectively. Botulin toxin type C was found in a considerable number of serum samples, accounting for 40.48% (51/126). Meanwhile, the percentage of serum samples containing botulin toxin types E and D was 28.57% (36/126) and 25.40% (32/126), respectively. Clostridium botulinum was detected in the farming environment specifically 17.5% (105/600) in soil, 19.67% (118/600) in water, 8.33% (18/216) in crabs, and 3.00% (12/400) in snails. Conclusion: The free-range ducks in the Mekong Delta were at high risk of botulism because of the latent presence of C. botulinum in the farming environment.