Hyporheic groundwater geochemistry evolution depends on the interactions of surface water and groundwater (SW–GW). Hydrodynamic variations driven by the long-term managed aquifer recharge (MAR) practice could change hyporheic geochemical processes, which requires a better understanding for groundwater management. In this work, a geochemical survey was conducted in a multi-aquifer MAR system. The results showed great impact of the MAR practice on the hydrodynamics and major ion chemistry of groundwater in the hyporheic zone compared to natural recharge. Besides, related geochemical processes including rock weathering and ion exchange showed increased effect on hyporheic hydrochemistry with aquifer depth, depending on hydrogeological conditions in addition to river water infiltration. Combined with hydrochemical indicators and the end-member mixing model, the relative contribution of precipitation to groundwater was estimated to be 5% for the 30-m aquifer, 16% for the 50-m aquifer, and 64% for the 80-m aquifer. However, precipitation made small contributions (<5%) to the major ions of groundwater regardless of depth. Conversely, the relative contributions of river water infiltration decreased with aquifer depth (95%→84%→36%), and its proportional contributions to major ions showed a similar trend (90%→84%→39%), which suggests reduced SW–GW interaction intensity with depth in the hyporheic zone. The major ion compositions of hyporheic groundwater tend towards river water after the long-term MAR practice, reflecting comprehensive effect of mixing and related geochemical processes. This study demonstrates the relevance of detailed studies at regional scale to understand anthropogenic effects from projects such as MAR on groundwater geochemistry especially in multi-aquifer systems.