The Late Ordovician (Katian-Hirnantian) through earliest Silurian (Rhuddanian) interval was a time of varying climate and sea level, marked by a peak glacial episode in the early-mid-Hirnantian. Synthesis of recently published data permits global correlation of at least two cycles of glacial advance and retreat with a distinct interglacial period that is recognizable in sequence-stratigraphic and chemostratigraphic records in many parts of the world. A period of warming and sea-level rise during the late Katian is marked by the widespread occurrences of oceanic anoxia in paleotropical and subtropical localities, mostly confined to regions of inferred upwelling and semirestricted marine basins. Nitrogen isotope data show that the regions of oceanic anoxia were marked by intense water-column denitrification in which cyanobacteria were the principal source of fixed N. In the overlying peak glacial interval of the Hirnantian, sedimentary successions from localities representing a wide range of water depths and paleolatitudes indicate that anoxia was restricted during the early-mid-Hirnantian. The shift to more positive N isotope values also suggests less intense water-column denitrification. In the overlying late Hirnantian and early Rhuddanian, the distribution of black shales reaches its greatest extent in the studied interval. Localities showing evidence of anoxia are globally spread over all paleolatitudes and water depths for which data are available, indicating a Rhuddanian ocean anoxic event comparable to examples from the Mesozoic. It is accompanied by a return to intensely denitrifying conditions within the water column, as indicated by the shift to negative N isotope values. The two phases of Hirnantian mass extinction coincide with rapid, climate-driven changes in oceanic anoxia. The first extinction occurred at the onset of glaciation and with the loss of anoxic conditions at the end of the Katian. The second extinction occurred at the demise of glaciation and coincided with the return of anoxic conditions during the late Hirnantian–early Rhuddanian. Integration of our N isotope data with graptolite biodiversity records suggests that the extinctions were profoundly influenced by changes occurring at the base of the marine food web, i.e., redox-driven changes in nutrient cycling and primary producer communities.