This study aimed to analyze the temporal trends and spatial distribution of mortality from malignant central nervous system (CNS) neoplasms in Brazil from 2000 to 2023. An ecological, time-series study using Joinpoint regression for temporal analysis and Global and Local Moran’s I for spatial patterns. Data were retrieved from the Mortality Information System (SIM). A total of 187,551 deaths were recorded. The Average Annual Percent Change (AAPC) showed a significant growth of +2.1% (95% CI: 1.8 – 2.4). However, a significant inflection point was identified in 2013; between 2000–2013, the APC was +4.1% (p < 0.05), becoming non-significant (+0.8%) thereafter, likely reflecting methodological data inconsistencies in the national system. Spatially, high-high clusters were concentrated in the South and Southeast regions (Moran’s I p < 0.05), while the North and Northeast presented low-low clusters, suggesting significant underreporting. While mortality trends appear to increase, they are heavily influenced by regional diagnostic disparities and information system transitions. This is the first nationwide study to integrate spatio-temporal dynamics to highlight these inequities in Brazil.