The evolution of Ordovician cephalopod diversity in the Middle Yangtze region of South China has been analysed. The cephalopods in this region appeared in the earliest Tremadocian, radiated in the Early-Middle Floian and Middle Ordovician, and went through an extinction period during the Late Katian and Hirnantian. The composition of the cephalopod fauna underwent major changes in the Late Floian. Specifically, all the genera occurring in previous time periods disappeared and Tarphyceratida, Actinoceratida, and Orthoceratida appeared and prospered. Differences in the evolution of cephalopod diversity between Middle Yangtze region and other regions were detected, which were caused by differences in the vertical sequence and horizontal combination of controlling factors. Changes in living environments and the distribution of food resources prompted Ordovician cephalopods to evolve adaptations for life in deep-water environments. The low-temperature ocean current near the western coastline of Gondwana created favourable conditions for the Floian peak of cephalopod diversity in South China. The tectonic movements, high rainfall, and relatively closed environment of the Middle Yangtze region led to rapid sea level rise and hindered cephalopod diversification. These processes explain the low cephalopod diversity in the Late Ordovician and the absence of the previously reported Katian radiation peak in this region.