The present study investigates the processes controlling the elementary and isotopic cycle of the lithium over the Amazon basin. A numerical model is developed to simulate two major processes that have been proposed as key controls of the river lithium isotopic composition: weathering reactions inside the regolith, accounting for secondary phase formation, and interactions between riverine water and secondary phases in floodplain. Both processes generate fractionation of lithium isotopes ("batch" fractionation and "Rayleigh" distillation respectively) that potentially control the riverine isotopic composition of the Amazon and its tributaries. A study of the model parameters shows that two different regimes are impacting the lithium isotopic composition of the rivers within the Amazon catchment. In the South (Madeira and its tributaries), the lithium isotopic signature of river waters can be explained by lithium release and fractionation during weathering reactions in the regolith, followed by "Rayleigh distillation" in the floodplain increasing progressively the lithium isotopic composition, in agreement with a previously published hypothesis. In contrast, the lithium isotopic composition of rivers located in the northern part of the Amazon watershed (Solimoes and tributaries) cannot be simulated by the model assuming the same processes than in the southern part. Model optimization suggests than the nature of the material being eroded and weathered is important. In the North, fresh source rocks of volcanic origin releases large amount of Li and promotes rapid smectite precipitation, allowing the riverine δ 7 Li to rise before flowing through floodplains. This result suggests that the environments able to generate high riverine δ 7 Li (higher than 25‰) are complex and not firmly identified yet.