Recent eustatic reconstructions allow for reconsidering the relationships between the fifteen Paleozoic–Mesozoic mass extinctions (mid-Cambrian, end-Ordovician, Llandovery/Wenlock, Late Devonian, Devonian/Carboniferous, mid-Carboniferous, end-Guadalupian, end-Permian, two mid-Triassic, end-Triassic, Early Jurassic, Jurassic/Cretaceous, Late Cretaceous, and end-Cretaceous extinctions) and global sea-level changes. The relationships between eustatic rises/falls and period-long eustatic trends are examined. Many eustatic events at the mass extinction intervals were not anomalous. Nonetheless, the majority of the considered mass extinctions coincided with either interruptions or changes in the ongoing eustatic trends. It cannot be excluded that such interruptions and changes could have facilitated or even triggered biodiversity losses in the marine realm.