Groundwater salinity hotspots in shallow aquifers have been reported across various geographical and climatic settings. These hotspots are commonly linked to anthropogenic influences, particularly irrigation return flow, in arid, unconfined aquifers under intensive irrigation. However, the interplay of geological and hydrochemical processes in shaping salinity variation and hotspots formation remains insufficiently understood. This study integrates hydrochemical, isotopic, multivariate statistical, and geophysical methods to better understand the regional distribution and origin of groundwater hotspots in the newly reclaimed areas of the Eastern Sahara, along the desert fringes of the Nile River. The findings suggest that salinization in the aquifer is influenced by evaporite dissolution, silicate weathering, salts leaching, ion exchange, and groundwater mixing processes, with significant anthropogenic contributions from irrigation return flow and fertilizer application. Notably, we report for the first time that salt-rich marine clay layers, which were left unflushed during the evolution of the Nile River, serve as the primary source of salinity hotspots. These clay layers act as natural barriers, restricting groundwater exchange with the Quaternary Nile aquifer while promoting salinization through saline/formation water upconing due to excessive groundwater pumping. Furthermore, inefficient irrigation practices add more water through irrigation return flow to the sandy alluvium aquifer, which exacerbates the groundwater salinity and ultimately leads to the development of waterlogged areas. These findings highlight the significant impact of river system evolution dynamics on groundwater quality and call for revisiting the current irrigation strategies in the newly reclaimed areas along the Nile River's desert fringes.