1. Opisthorchis viverrini is a water-based disease-causing parasite whose public health implications are relevant in particular in Southeast Asia despite broad control efforts and education campaigns. Untreated or chronic infections often lead to severe hepatobiliary morbidity including cholangiocarcinoma, an often lethal bile duct cancer. The liver fluke O. viverrini is the causative agent of opisthorchiasis, and can be contracted by consumption of raw fish, after which it settles in the small intrahepatic bile ducts. The life cycle involves, besides freshwater snails in which asexual reproduction takes place, freshwater cyprinid fishes (family Cyprinidae) as intermediate hosts. Piscivorous mammals, including humans, dogs and cats, act as definitive hosts. 2. Here, we propose a spatially explicit model for the transmission dynamics in realistic freshwater environments. Our model generalizes existing mathematical models, in particular by assimilating novel types of spreading mechanisms in space and time. We explore theoretically the range of outcomes that the proposed framework produces, and its basic sensitivity and stability analyses; 3. Our study emphasizes that hydrological connectivity is key to shaping patterns of disease spread. Fish distribution and mobility also affect disease inroads. Our study provides baseline information on the role of connected freshwater bodies and their suitability for intermediate and final hosts. The distributions of fish catch and fish market supplies are also considered because they affect the spatiotemporal spread of opisthorchiasis; 4. Adding a spatial resolution to transmission models changes fundamentally the epidemiological descriptions and the related scenarios of disease propagation and allows an improved description of the ecology of hosts, parasites, and their infection cycles. 5. The improvement that the work provides is a much more realistic description of the environment where infection cycles develop and spread, reflected in the inclusion of relevant, hitherto neglected, epidemiological factors.