This thesis presents new micropalaeontological and geochemical palaenvironmental proxy data through the late Eocene into the earliest Oligocene from a clay-rich succession from the US Gulf Coast. It is based on samples from the Yazoo Clay Formation, recovered in the Mossy Grove Core near Jackson, Mississippi. This represents an apparently continuous section of relatively uniform lithology, clay-rich deposits, that host very well preserved assemblages of calcareous nannofossil, foraminifera and organic biomarkers. This thesis makes use of these to generate a detailed calcareous nannofossil taxonomy, high-resolution calcareous nannofossil assemblage data and coccolith-fraction bulk isotope data, as well as pilot planktonic foraminifera abundance and isotope records. It also develops pilot data for organic: biomarkers that demonstrate the presence and utility of biomarker proxies for ancient sea surface temperatures within the Yazoo Clay. The results of this project characterize the late Eocene US Gulf Coast as a sub-tropical shelf sea environment that experiences several stages of sea surface cooling and increasing nutrient contents — potentially linked to sea level fall — in the late Eocene and earliest Oligocene. The most important finding of this project is evidence for cooling and major perturbations to the climate-carbon cycle significantly before the onset of the major phases of Antarctic glaciation.