Understanding the mechanism of geogenic arsenic mobilization from sediments to groundwater is important for safe and sustainable drinking water supply in the central Yangtze River Basin. Unlike the preponderance of observations within the deltas of South and Southeast Asia, groundwater As concentrations in the Holocene and upper Pleistocene aquifers at Yangtze vary by up to an order of magnitude seasonally. Bulk sediment geochemistry, arsenic associated mineralogical analysis and high-resolution OSL dating were applied to decipher the sedimentological controls on the formation of high arsenic aquifers. Sedimentological processes and paleoclimatic optima after the Last Glacial Maximum (LGM) have created favorable conditions for the formation of high-As aquifer systems. Intensive chemical weathering leading to sulfur depletion after the LGM could facilitate As enrichment in the Holocene and upper Pleistocene aquifers. Arsenic release depends on the iron mineralogy and microbial community in the aquifer sediments. Results of batch experiments and reactive transport modeling indicated that seasonal changes in surface water and groundwater levels drive changes in redox conditions. Seasonal variation of biogeochemical iron redox cycle may essentially control the mobilization/immobilization of As, while bacterial sulfate reduction could cause temporal attenuation of groundwater As concentration.