The Cretaceous provides us with an excellent case history of ocean-climate-biota system perturbations. Such perturbations occurred several times during the Cretaceous, such as oceanic anoxic events and the end-Cretaceous mass extinction, which have been the subject of an abundant literature. Other perturbations, such as the mid-Maastrichtian Event (MME) remain poorly understood. The MME was associated with global sea-level rise, changes in climate and deep-water circulation that were accompanied by biotic extinctions including ‘true inoceramids’ and the demise of the Caribbean-Tethyan rudist reef ecosystems. So far, the context and causes behind the MME remain poorly studied. We conducted high-resolution integrated biotic, petrological and geochemical studies in order to fill this knowledge gap. We studied, in particular, carbonate Nd and Os isotopes, whole-rock Hg, C and N content, C and N isotopes in organic matter, S isotopes in carbonate-associated sulfate, along with C and O isotopes in foraminifera from the European Chalk Sea: the Polanówka UW-1 core from Poland and the Stevns-1 core from Denmark. Our data showed that sea-level rise of ∼50–100 m lasted around ∼2 Ma and co-occurred with anomalously high mercury concentration in seawater. Along with previously published data, our results strongly suggest that the MME was driven by intense volcanic–tectonic activity, likely related to the production of vast oceanic plateaus (LIP, Large Igneous Province). The collapse of reef ecosystems could have been the consequence of LIP-related environmental stress factors, including climate warming, presumably caused by emission of greenhouse gases, modification of the oceanic circulation, oceanic acidification and/or toxic metal input. The disappearance of the foraminifer Stensioeina lineage on the European shelf was likely caused by the collapse of primary production triggered by sea-level rise and limited amount of nutrient input. Nd isotopes and foraminiferal assemblages attest for changes in sea-water circulation in the European Shelf and the increasing contribution of North Atlantic water masses.