The connections between the depositional environment, sediment chemistry, and pore structure of deep-water mudstones are still not completely understood. This study: 1) investigates the sediment chemistry and the depositional conditions of the Pennsylvanian Cline Shale chemofacies in the center of the Midland Basin, 2) characterizes the conditions favorable to organic matter accumulation of each mudstone chemofacies, and 3) examines the connection between the pore structure and the mudstones’ paleo-environmental and paleo-geochemical context and processes. This study uses X-ray fluorescence (XRF) and statistical methods (Isolation Forest, Principal Component Analysis, and K-means) to identify four chemofacies of 127 m of Cline Shale core from the Matthew 'D' 0906 well located in the Midland Basin depocenter in Glasscock County, Texas. In addition, petrographic and scanning electron microscopy and measurements by dual-energy computed tomography, X-ray diffraction, Rock-Eval pyrolysis, N2 isothermal adsorption tests, and mudrock reservoir properties were conducted on thin-sections, core slabs, and samples to understand the bulk geochemistry and petrophysical properties of the mudstones. Four chemofacies are identified: (1) Siliceous Mudstone with high Zr and low Ca and P, (2) Calcareous-argillaceous Mudstone I with high Ca and Zr, and low P, (3) Argillaceous Mudstone with high P and low Ca and Zr, and (4) Calcareous-argillaceous Mudstone II with high Ca and P, and low Zr. Based on elemental distribution, the first two and last two chemofacies are interpreted as low sea-level deposits and high sea-level deposits, respectively. Water stratification and P regeneration accounted for the highest total organic carbon (TOC) content, which resulted in the high porosity and pore volume of the low sea-level Siliceous Mudstone chemofacies, especially visible in the 8 nm–186 nm organic matter pores. Carbonate input hinders the development of the inorganic pore system, especially for organic lean Calcareous-argillaceous Mudstones. Nine sea-level cycles were observed in the cores and correlated to nine US mid-continent cycles attributed to the 405-kyr Milankovitch parameter (long orbital eccentricity) during the late Pennsylvanian. We hypothesize that late Pennsylvanian climate change, paced by orbital cycles, controlled the distribution and stacking pattern of mudstone chemofacies, which also controlled source rock quality and consequent pore system development.