Background. Malaria remains a significant public health challenge in Mali, particularly in endemic areas such as the Kolondieba health district. This study aimed to analyse the geo-temporal dynamics of clinical malaria transmission, identifying high-risk periods, vulnerable age groups and associated environmental and health determinants. Materials and Methods. A historical cohort study was conducted from 2019 to 2021 across 21 health facilities in the Kolondieba district. Epidemiological, climatic, and demographic data were analysed using geospatial tools (QGIS) and statistical software (R). The non-parametric Wilcoxon and Kruskall-Wallis tests were used to compare two means and population malaria incidence distribution, respectively. Results. The incidence of malaria exhibited seasonality influenced by precipitation and humidity, while elevated temperatures were associated with a decrease in malaria incidence. Periods of high transmission potential (HTP) last for 20-25 weeks annually (weeks 23-48) and peak around weeks 30-31. Malaria accounted for 53.71% of consultation reasons, with pronounced vulnerability observed in children aged 0-4 yrs, especially during high transmission periods. Spatial stratification revealed two risk levels: 5 health areas at moderate risk (incidence 251-450 cases/1000 inhabitants) and 16 at high risk (>450 cases/1000 inhabitants). Health center attendance was a more determining risk factor. Conclusion. This study highlights the spatial and temporal heterogeneity of malaria transmission in southern Mali, emphasising the necessity to target interventions during weeks 23-48 (June through November), among children <5 yrs of age, in health areas with high health centre attendance. The integration of socio-economic factors in future studies could refine control strategies.