Profound changes are occurring to hydrological processes in semi-arid environments. For water resources to be managed sustainably these changes and their drivers need to be understood. This study focusses on the anthropogenic alteration of river-aquifer interactions in the Murray Darling Basin, Australia. Field investigations were carried out on a floodplain of the Namoi River. Naturally occurring stable isotopes of water in combination with hydrometric data were used to understand the river-aquifer interactions. Two end-members are established: a regional isotopically depleted groundwater signature, and an evaporatively enriched river water signature. Water at depth in the aquifer and away from the river has the depleted signature indicative of water originating from rainfall, while water in the upper aquifer and close to the river has elevated δ18O values indicative of water originating from the river. The hydrometric data suggest that groundwater flow towards the river in the upper aquifer has reduced in magnitude while flow in the lower aquifer has reversed in direction since development. It is found that when there is no river flow or groundwater abstraction there is little interaction, while when there is river flow or abstraction recharge from the river is induced. It is further found that the river is complexly connected to groundwater abstraction. Abstraction from the lower aquifer is causing extensive declines in groundwater levels in that aquifer, which in turn is causing an increased vertical leakage of water from the upper to the lower aquifer. This leakage is causing declines in groundwater levels in upper aquifer and thus an increased lateral infiltration of river water to the upper aquifer during flow events. The study illustrates that conventional concepts for surface water groundwater interactions can be too simplistic and that a solid understanding of the site geology is a perquisite for better understanding of the interaction processes.