<p>Soil contamination by potentially harmful elements (PHEs) has become a pressing environmental concern in arid and semi-arid regions, where natural processes and human activities intensify the accumulation of these elements. Understanding the spatial variability, contamination and eco-toxicological implications of PHEs is vital for safeguarding ecosystem integrity, biodiversity and public health. This study highlights the need for a comprehensive analysis of the contamination levels, spatial distribution, potential sources and eco-toxicological status of PHEs in soils across various land-use types in the Sistan Basin, eastern Iran. Soil samples were analyzed for PHEs to assess the contamination factor (C_f), pollution load index (PLI), and ecological risk, supported by spatial mapping and health risk assessment. Results revealed that aluminum (Al) and iron (Fe) were major elements sourced from geogenic origin, whereas cadmium (Cd), arsenic (As), and lead (Pb) exhibited considerable enrichment in agricultural lands and dusty roads due to the use of agrochemicals, fertilizers, vehicle emissions and combustion activities. C_f values indicated low contamination in most sites, while PLI generally revealed low soil pollution levels. Based on Håkanson’s classification, Cd was identified as the principal contributor to ecological risk. Health risk assessment revealed ingestion as the primary exposure route, with children being more vulnerable than adults, while non-carcinogenic and cancer risks remained within acceptable ranges, although the health risks in agricultural and dusty road zones suggest potential long-term effects. The integration of contamination indices, geospatial mapping, ecological and health risk underscores the importance of sustainable agricultural practices, regular monitoring and strategic management in conserving soil quality and wetland ecosystems in Sistan.</p>