Mapping the Middle to Upper Pleistocene Rhine–Meuse sequence in the southern North Sea based on new core and seismic data has allowed a detailed palaeoenvironmental re-assessment. An integrated seismo-lithostratigraphic and malacological biostratigraphic framework is correlated with the optically stimulated luminescence-dated Rhine–Meuse sequence onshore. The data point to a dynamic interplay of fluvial and marine systems in the southern part of the North Sea driven by longer-term (>100 ka) tectonic and epeirogenic processes and shorter-term (<10 ka) climatic processes. The final permanent breaching of the Cretaceous chalk at the Strait of Dover during the Saalian (Marine Isotope Stage 6, MIS 6) ice age led to the formation of the ‘Eurogeul’ belt, a gravelly sand belt that represents the largest concentration of gravelly fluvial sediments in the southern North Sea. The formation and preservation of the Rhine–Meuse sequence is related to long-term (>100 ka) uplift of the Wealden–Artois synclinorium and compaction-driven subsidence of Tertiary shales within the Voorne Trough. The dominant erosive sedimentary signatures within the Rhine–Meuse sequence resulted through shorter-term (<10 ka) interplay of Pleistocene transgressions, glaciations and the permanent breaching of the Cretaceous chalk at the Strait of Dover by the Palaeo-Channel river during the Saalian (MIS 6).