Background: Malaria transmission persists in Sahelian West Africa, with asymptomatic Plasmodium falciparum infections acting as a reservoir. Yet malaria epidemiology and research focus heavily on clinical cases. It remains unclear whether parasites causing clinical infections are genetically representative of the asymptomatic reservoir. Methods: A one-year cohort study (2021 and 2022) was conducted in four villages in the Kedougou district of Senegal and two villages in the Kati district of Mali, collecting 1,133 P. falciparum-positive samples from asymptomatic and clinical infections. Using parasite molecular barcodes and whole-genome sequencing, we estimated multiplicity of infection (MOI), runs of homozygosity (RoH), and identity-by-descent (IBD) to compare parasite populations between infection types and across age groups. Results: A total of 226 whole genomes and 728 barcodes were analysed, representing 78.2% (570/729) of clinical cases and 21.7% (158/728) of asymptomatic infections. MOI was high, with over 50% of infections being polyclonal, and did not differ by age or infection status. IBD analysis revealed a highly diverse parasite population, with transmission clusters including both asymptomatic carriers and clinical cases. Drug resistance allele frequencies were similar between groups. Conclusion: Overall, we found no evidence of genetic differentiation between parasites from clinical and asymptomatic infections, suggesting that clinical cases reflect the broader parasite population sustaining transmission. These findings provide a basis for linking genomic metrics with epidemiological factors and for monitoring the impact of future interventions on the parasite population.