The early Paleogene is critical for understanding global biodiversity patterns in modern ecosystems. During this interval, Southern Hemisphere continents were largely characterized by isolation and faunal endemism following the breakup of Gondwana. Africa has been proposed as an important source area for the origin of several marine vertebrate groups but its Paleogene record is poorly sampled, especially from sub-Saharan Africa. To document the early Paleogene marine ecosystems of Central Africa, we revised the stratigraphic context of sedimentary deposits from three fossil-rich vertebrate localities: the Landana section in the Cabinda exclave (Angola), and the Manzadi and Bololo localities in western Democratic Republic of Congo. We provide more refined age constraints for these three localities based on invertebrate and vertebrate faunas, foraminiferal and dinoflagellate cyst assemblages, and carbon isotope records. We find an almost complete absence of Danian-aged rocks in the Landana section, contrary to prevailing interpretations over the last half a century (only the layer 1, at the base of the section, seems to be Danian). Refining the age of these Paleocene layers is crucial for analyzing fish evolution in a global framework, with implications for the early appearance of Scombridae (tunas and mackerels) and Tetraodontiformes (puffer fishes). The combination of vertebrate fossil records from Manzadi and Landana sections suggests important environmental changes around the K/Pg transition characterized by an important modification of the ichthyofauna. A small faunal shift may have occurred during the Selandian. More dramatic is the distinct decrease in overall richness that lasts from the Selandian to the Ypresian. The Lutetian of West Central Africa is characterized by the first appearance of numerous cartilaginous and bony fishes. Our analysis of the ichthyofauna moreover indicates two periods of faunal exchanges: one during the Paleocene, where Central Africa appears to have been a source for the European marine fauna, and another during the Eocene when Europe was the source of the Central Africa fauna. These data indicate that Central Africa has had connections with the Tethyian realm.