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Context: Neglected Tropical Diseases (NTDs) are infectious illnesses prevalent in tropical and subtropical regions, disproportionately affecting vulnerable populations with limited access to healthcare. Understanding the spatial and temporal dynamics of these diseases in specific regions, such as northern Brazil, is crucial for guiding control strategies. The state of Pará, characterised by low human development indices, is a significant hotspot for NTDs. Development: This cross-sectional study analysed the spatio-temporal distribution of major autochthonous NTDs in Pará between 2016 and 2022, using data from Brazil’s Notifiable Diseases Information System (SINAN). Incidence rates were calculated for dengue, Chagas disease, leishmaniasis (cutaneous and visceral), leprosy, tuberculosis, and schistosomiasis, and used to generate spatial cluster maps. Results: The analysis revealed patterns of clustering and dispersion, with high-risk areas identified in the Southeast (Carajás), Marajó, and Belém Metropolitan regions. Cutaneous leishmaniasis was widespread in Marajó and southwestern Pará, while visceral leishmaniasis was concentrated in the southeast. Leprosy remained prevalent in urban and peri-urban zones, and schistosomiasis persisted in riverside communities. The Southeast region showed a high burden of four NTDs. Conclusion: Spatio-temporal analysis of NTDs in Pará revealed geographic clusters, socio-environmental influences, and diagnostic gaps, guiding targeted, adaptive public health strategies and future research priorities.