The Kupferschiefer districts in Central Europe contain some of the world’s largest sediment-hosted stratiform Cu deposits. The fine-grained sulfides are hosted by the Rotliegend sandstone (S1), organic matter-rich Kupferschiefer (T1) mudstones and Zechstein Limestone (Ca1). In this study, standard and high-resolution microscopy techniques (reflected-transmitted light, SEM, FIB-TEM) are combined with quantitative mineralogical data (X-ray diffraction, QXRD) to characterize the key mineral assemblages and styles of sulfide mineralization in drill core samples from different localities (Sangerhausen, Allstedt, Wallendorf) of the Saale subbasin, Eastern Germany. Our QXRD data show a progressive decrease in calcite abundance from the underlying S1 into the T1 in the Sangerhausen and Allstedt drill cores and an upward increase in calcite in the Wallendorf drill core. Petrographic data show extensive in situ alteration of rock fragments and detrital feldspar in the S1. Diagenetic calcite has formed intergranular pore-filling cement that occludes primary porosity in the S1 and T1. The ore-stage sulfides (bornite, sphalerite, galena, ± pyrite) in the S1 and T1 are mostly formed as a replacement of calcite cement and, to a lesser extent, feldspar. High-resolution TEM data has helped to identify hematite and magnetite within particular calcite growth zones in the S1, which likely corresponds with the “Rote Fäule” alteration associated with the Cu sulfide mineralization. Nanoscale Cu-chloride complexes have also been identified, intergrown with pore-filling illite in the T1. In summary, the distribution and dissolution of calcite cement were critical to the secondary porosity development and migration of the mineralizing fluids in the Saale subbasin.