Southern Iceland is one of the main outlets of the Icelandic ice sheet and is subject to seismicity of both tectonic and volcanic origins along the South Iceland Seismic Zone (SISZ). A sedimentary complex spanning Marine Isotopic Stage 6 (MIS 6) to the present includes evidence of both activities. It includes a continuous sedimentary record since the Eemian interglacial period, controlled by a rapid deglaciation, followed by two marine glacioisostasy-forced transgressions, separated by a regression phase connected to an intra-MIS 5e glacial advance. This record has been constrained by tephrostratigraphy and dating. Analysis of this record has provided better insights into the interconnectedness of hydrology and volcanic and tectonic activity during deglaciations and glaciations. Low-intensity earthquakes recurrently affected the water-laid sedimentation during the early stages of unloading, accompanying rifting events, dyke injection, and fault reactivations. During full interglacial periods, earthquakes were significantly less frequent but of higher magnitude along the SISZ, due to stress accumulation, favored by low groundwater levels and more limited magma production. Occurrence of volcanism and seismicity in Iceland is commonly related to rifting events. Subglacial volcanic events seem moreover to have been related to stress unlocking related to limited or full unloading/deglaciation events. Major eruptions were mostly located at the melting margin of the ice sheet.