Detailed lithostratigraphic and calcareous nannofossil biostratigraphic studies were carried out across the Paleocene–Eocene (P-E) that outcrops at Gebel Nezzazat (G. Nezzazat) in West Central Sinai (Egypt). The study interval spans from the upper part of the Tarawan Formation to the lowermost Thebes Formation covering the whole Esna Formation in between them. The Esna Formation had been subdivided into four members: the Hanadi, Dababiya Quarry, Mahmiya, and Abu Had Members. Five calcareous nannofossil biozones (NP7/8, NP9 to NP12) and four subzones (NP9a and NP9b and NP10a and NP10b) were recognized. The lowest occurrences (LOs) of Fasciculithus alanii group, Neochiastozygus junctus, Sphenolithus radians, and Blackites herculesii as well as the highest occurrence of F. alanii group and the increased frequency of N. junctus are biostratigraphically significant. On contrast, the LOs of Discoaster binodosus, Discoaster mahmoudii, Discoaster diastypus, Zygrhablithus bijugatus, and Campylosphaera dela as well as the LOs of Fasciculithus tympaniformis are unreliable bioevents. Calcareous nannofossils increase in abundance close to the P-E transition. Ericsonia subpertusa suddenly increases above the base of Eocene, whereas the diversity of Fasciculithus drops close to this level. The P-E boundary at G. Nezzazat was placed at the base of the Dababiya Quarry Member in coincidence with the base of Subzone NP9b that was delineated by the LOs of Discoaster araneus, Rhomboaster cuspis, Rhomboaster calcitrapa, Rhomboaster spineus, and Rhomboaster bitrifida. A small gap was recorded across the P-E boundary as indicated by the lack of the four beds of the Dababiya Quarry Member. The changes in calcareous nannofossil assemblages reveal warm-water and oligotrophic conditions prevailed during the transition at G. Nezzazat.