(1) Background: Mercury and lead contamination resulting from various anthropogenic activities represents a global environmental problem and a considerable risk to the health of the human population. (2) Methods: The objective of this research was to evaluate the concentrations of mercury (Hg) and Lead (Pb) in the blood of the child population in the municipalities in the Atrato River basin using a direct Hg analyzer and graphite furnace atomic absorption spectrometry. (3) Results: In total, 171 children (5–14 years of age) were taken into account, and 18.71% (32) of the children had concentrations of Hg and Pb above the permissible values established by the WHO. In the municipality of UN, 19 children had blood Hg concentrations between 5.29 and 17.71 μg/L. In CA, two children had concentrations of 5.03 and 8.43 μg/L, separately. In the case of Pb, seven children showed concentrations between 3.60 and 4.83 μg/dL in the municipality of RQ, three in UN (3.59, 3.61, and 4.60 μg/dL), and one in Carmen de Atrato (5.47 μg/dL). (4) Conclusions: The levels of Hg and Pb in the blood of children living in the riparian areas of the Atrato River basin are related to gold mining activities in the basin and the consumption of contaminated fish.