To analyze the spatial-temporal distribution and factors associated with mortality from neglected tropical diseases (NTDs) in Brazil from 2000 to 2019.We performed an ecological study to analyze NTD-related deaths recorded in the Ministry of Health Mortality Information System (SIM). For the temporal analysis, the joinpoint method was used. Spatial dependence was analyzed using global Moran and local Getis-Ord Gi* indices. Four non-spatial and spatial regression models were used to identify factors associated with mortality.The mean mortality rate from NTDs in Brazil during the study period was 3.32 deaths per 100 000 inhabitants, with the highest rate (8.68 deaths per 100 000 inhabitants) recorded in the Midwest. The most prevalent causes of death were Chagas disease (n = 94 781; 74.9%) and schistosomiasis (n = 10 271; 8.1%). There was a 1.24% reduction (95%CI = -1.6; -0.9; P 2 people per bedroom" (β = -0.07; P = 0.00) and "municipal human development index" (β = -3.36; P = 0.08) were negatively associated with the outcome, while the "index of social vulnerability" (β = 2.74; P = 0.05) was positively associated with the outcome.Lower human development and higher social vulnerability are associated with higher mortality from NTDs, which should guide NTD prevention and control efforts.