The Opalinuston-Formation in Southern Germany comprises a thick sequence of Middle Jurassic silty claystones. In parts of Bavaria and Baden-Württemberg, the formation has been designated as a sub-area by the Federal company for radioactive waste disposal (BGE), indicating that favorable geological conditions for the final disposal of high-level radioactive waste can be expected there. However, state-of-the-art sedimentological and stratigraphic data for the complete formation is typically lacking. This contribution provides new and coherent data on the geological variability of the Opalinuston-Formation in Southern Germany based on four drill cores that penetrated through the entire formation. Cores were examined in high resolution using a combination of classic core description techniques, non-destructive analytical tools such as XRF core scanner and high-frequency sampling for a precise stratigraphic classification and geochemical-mineralogical characterization. Particularly with respect to changes in grain size, clay mineralogy and sedimentary facies, results exhibit both, notable variability but also similarities between sites, and in comparison to observations from Switzerland. Such sedimentological and stratigraphic patterns can be explained by the interplay of a complex, bottom-current dominated depositional environment, and differential subsidence, leading to relative-sea-level changes on a sub-basin scale. In summary, this contribution highlights the geological variability of the Opalinuston-Formation in Southern Germany and beyond, and discusses the possibilities of a sequence stratigraphic approach to accelerate exploration efforts of siting regions in claystone formations in order to rapidly identify the most suitable parts for the final disposal of high-level radioactive waste.