The worldwide latest Cenomanian Oceanic Anoxic Event 2 (OAE2) was investigated for the planktonic foraminiferal assemblages in the type area of its sedimentary expression, the Corg–rich Bonarelli Level (Gubbio, central Italy). The 313 kyr preceding the onset of OAE2 and the 153 kyr following the end of this event were analyzed in the deep-water setting of the Bottaccione section (Umbria-Marche Basin). For the first time, a high-resolution approach and quantitative methods were applied. Several events and biotic changes, including the acme and crisis of different genera, were recognized. They provide evidence of a progressive and rapid deterioration of paleoenvironmental conditions, reaching a climax coincident with the Bonarelli Event, and of the subsequent, gradual (although not complete) recovery. Although no major mass extinction in planktonic foraminifera occurred across the Bonarelli Event, the extinction of the most specialized forms, i.e., the rotaliporids, and Globigerinelloides bentonensis, is recorded just before its onset. The observed pattern of marked changes in planktonic foraminiferal assemblages indicates five discrete phases of different degrees of environmental perturbation within the marine ecosystem. Phase I (313–55 kyr prior to the onset of OAE2) is characterized by a high planktonic foraminiferal abundance and diversity that imply a relatively stable environment, with different ecological niches occupied and stratified water column. On the other hand, relatively high percentages of hedbergellids and heterohelicids indicate a general mesoeutrophic environment and a well-developed oxygen minimum zone. Episodes of increased eutrophic conditions are indicated by pulses in abundance of radiolarians. A well-developed oxygen minimum zone may be related to a long-term change that precedes the onset of OAE2 (mid-Cenomanian Event). The most dramatic changes took place during Phase II and encompassed the last 55 kyr preceding deposition of the Bonarelli Level. The onset of a high-stress environment is clearly shown by the shift to a distinctly unstable planktonic foraminiferal structure, characterized by low species diversity and marked foraminiferal changes and events. Some of these took place at the same time (the rotaliporid crisis, the heterohelicid decline, the Hedbergella-Schackoina shift, the onset of the ‘large form eclipse’ when > 150 μm forms temporarily disappeared) followed by other sequential events (onset of dwarfism, schackoinid acme, and hedbergellid acme). The above-mentioned changes and events indicate for Phase II an increased surface productivity, enhanced oxygen minimum zone, and marked rapid changes of ecological parameters (e.g., temperature, salinity, trace metals). These marked foraminiferal changes culminate at the base of the Bonarelli Level with the temporary disappearance of all planktonic foraminifera. Phase III (100–900 kyr) coincides with the Bonarelli Level deposition and is characterized by highly eutrophic conditions, as indicated by radiolarian proliferation. Phase IV (35 kyr), similar to phase II except for the absence of rotaliporids, is characterized by the proliferation of the opportunistic hedbergellids and schackoinids, indicating that the environment remained ecologically unstable. The end of ‘large form eclipse’ marks the base of Phase V. During Phase V (118 kyr), planktonic foraminiferal abundance and diversity return to values comparable to those of Phase I, showing the gradual recovery of the ecosystem. However, high numbers of hedbergellids and heterohelicids suggest that the environmental perturbation related to the Bonarelli Event did not end during this phase, but continued well beyond deposition of the organic-rich layers. Our analysis shows that, in deep-water settings, the severe paleoenvironmental perturbation induced by the Bonarelli Event led to assemblages dominated by the small-sized, opportunistic hedbergellids and schackoinids. At the same time, the small-sized and presumably low-oxygen-tolerant, opportunistic heterohelicids underwent a marked decline. This scenario may be related to the exceptionally high-nutrient and low-oxygen content of the seawater, but also to variation of other ecological parameters. The perforate, elongated chambers and tubulospines of schackoinids may represent the best survivorship tool to have achieved better oxygen and nutrient uptake. We infer that schackoinids are useful indicators for extremely stressed environments in low- to middle-latitude, open-marine, deep-water settings during the Late Cretaceous.