The Hirnantian mass extinction is recognized as the first of the “big three” extinctions and, along with the end-Permian and end-Cretaceous events, is the result of an acceleration in biotic extinctions concomitant with a rise in originations. The Hirnantian mass extinction is characterized by high taxonomic impact and within-community extinctions. The Hirnantian mass extinction is also unusual in that (1) it is associated with glaciation, but there is little evidence elsewhere in the younger Phanerozoic that glaciations have been a cause of mass extinction, and (2) there is limited understanding of how glaciation could directly cause mass extinction, particularly in the marine realm. In this review, we argue that coordinated extinctions occurred at the onset and termination of glaciation and were due to climatically induced changes in relative sea level, ocean redox stratification, and sea-surface temperature gradients. These earth system changes resulted in a reduction in prospective niche space, both in the water column and on the seafloor, which in turn led to increased competition and selection pressures, resulting in extinctions where the carrying capacities of particular ecological niches were exceeded. The long-term ventilation of the oceans broke the link between glaciation and mass extinction.