Short-lived (104–105 years) carbon isotope excursions (CIEs), many of which are associated with some degree of ocean warming, are a feature of the warm climates of the early Paleogene. Here we present new calcareous nannofossil and geochemical data through the first of these Paleogene carbon cycle perturbations, known as the DAN-C2 event (65.8–65.7 Ma), from ODP Site 1049C on Blake Nose, in the western sub-tropical North Atlantic. Increased Hg/TOC (ppb/%) and Hg/Al (ppb/cps) ratios recorded at 65.9 Ma strongly suggest that volcanic activity, likely related to Deccan Traps, preceded the DAN-C2 event. Approximately 20 kyr after the onset of DAN-C2, Shannon diversity (H) index shows increased nannofossil species richness, with greater abundances of eutrophic and high fertility species, most likely a response to more intense weathering during the event. During the DAN-C2 event, there is a shift towards smaller morphotypes of the dominant placolith species, Coccolithus pelagicus and Cruciplacolithus primus, together with a calcium carbonate dissolution interval. Finally, we suggest that surface ocean currents dynamics, influenced by an eccentricity maxima cycle, is likely a potential mechanism to explaining the strong δ13C (∼1.3 ‰) negative excursion observed in Blake Nose.