Background Schistosomiasis is a persistent public health problem in Brazil. Regardless advances in diagnosis and mass treatment, schistosomiasis has a severe impact on morbimortality in the country and remains a neglected tropical disease. Herein, we assessed the basic and associated causes of schistosomiasis-related deaths and the temporal and spatial patterns of mortality from the disease in Brazil between 1999 and 2018. Methods We conducted an ecological and time series study. The segmented log-linear regression model was applied to assess time trends, considering all deaths recorded in the category B65/ICD-10. Additionally, we elaborated maps of mortality rates from schistosomiasis in Brazil. Results A total of 4168 schistosomiasis-related deaths were recorded in Brazil in this period, as an associated cause. Time trend analysis revealed an increase in the average age of deaths from schistosomiasis (annual percentage change (APC) = 0.84), and stable trend in Brazil (APC = 0.31). Concerning schistosomiasis-related deaths, we observed disorders related to the digestive system, liver diseases, septicemias, and chronic diseases. Surprisingly, there were deaths caused by non-endemic Schistosoma species in Brazil. Also, municipalities from non-endemic areas in Brazil presented schistosomiasis-related deaths. Conclusion Altogether, our analyses demonstrated that schistosomiasis remains a significant cause of death in Brazil, and it is increasing in some areas, especially in the Northeast region. Additionally, women and the elderly showed a stable time trend of deaths. Thereby, it urgently requires improvements in the control programs strategies, in the sense of an effective reduction in cases and deaths from the disease in Brazil.