In French Guiana were detected high lead (Pb) levels in blood of Amerindian people. Lead exposure is a serious hazard that can affect the cognitive and behavior development. People can be exposed to Pb through occupational and environmental sources. Fingerprinting based on stable Pb isotopes in environmental media is often used to trace natural and anthropogenic sources but is rarely paired with blood data. The objective of this study was to determine the main factors associated with high Blood Lead Levels (BLL). Soil, manioc tubers, food bowls, beverages, wild games, lead pellets and children blood were sampled in small villages along the Oyapock River. children BLL ranged between 5.7 and 35 µg dL−1, all exceeding 5 µg dL−1, the reference value proposed in epidemiologic studies for lead poisoning. Among the different dietary sources, manioc tubers and large game contained elevated Pb concentrations while manioc-based dishes were diluted. The isotopes ratios (207Pb/206Pb and 208Pb/206Pb) of children blood overlapped these of lead shots and meals. These first results confirm for the first time, the diary consumption of manioc-based food as the main contributor to Amerindian children’s BLL in French Guiana, but don’t exclude the occasional exposure to lead bullets by hunting activities. This is a specific health concern, since previous studies have shown that these same villagers present high levels of mercury (Hg). These communities are indeed subject to a double exposure to neurotoxic metals, Hg and Pb, both through their diet. The farming activity is based on manioc growing, and explaining that this ancestral practice can induce serious health risks for the child’s development may seriously affect their food balance and cultural cohesion.