Background: Schistosomiasis, after malaria, is the second most important parasitic disease in the world in terms of morbidity and mortality and is one of the 14 neglected tropical diseases. In 2016, about 206.4 million people needed preventive treatment for the disease. Objectives: This study evaluated schistosomiasis’s incidence rate and spatial-temporal cluster distribution in the north of Khuzestan province, Iran. Methods: This cross-sectional study collected data from January 1977 to December 2001. The data of 1,390 definitive patients with Schistosoma haematobium in the north of Khuzestan province, Iran, were analyzed for the disease incidence in rural districts over five-year periods. Also, the changes in median age and sex were examined. Spatial scan statistics were used to diagnose and evaluate the spatial clusters of S. haematobium cases. The pure retrospective temporal analysis and retrospective spatial-temporal analysis were carried out to identify the temporal clusters and spatial-temporal clusters of schistosomiasis with high rates, respectively, using the discrete Poisson model. Results: The schistosomiasis incidence decreased over the years, with the last case reported in 2001. Using Kulldorff’s spatial scan method, spatial clustering showed nine high-risk areas in the north of Khuzestan province from 1977 to 2001. Besides, S. haematobium was not randomly distributed in this area. Spatial-temporal clusters identified three high-risk areas during the study period. Temporal clusters decreased from 17 months and five days to one day, and they mainly occurred in the winter and summer. Conclusions: The study indicated a zero incidence and vanishing S. haematobium endemicity in the northern region of Khuzestan province of Iran in 2002. Due to snail vectors of the disease resident in this region, the disease surveillance still needs continuation.