The most prevalent Phanerozoic glaciation occurred during the Carboniferous–Permian on the Southern Hemisphere Gondwana supercontinent. Sediments from the Pennsylvanian Dwyka Group deposited in the Karoo Basin of South Africa provide a complete record of glaciation and deglaciation phases. The direct correlation of glaciation events in southern Gondwana basins with the well-studied climate evolution of equatorial regions was previously hampered by lack of precise radiometric dating. As dating has now become available for the Karoo Basin, the Gondwana glaciation can be viewed in a global paleoclimatic framework with high temporal resolution. Element geochemical proxies (CIA [chemical index of alteration], Zr/Ti, Rb/K, V/Cr) record three confined shifts in climate and paleoenvironment of the Karoo Basin. These shifts were induced by changes in sea level, weathering rate, provenance, and redox conditions. Because of the low availability and diagenetic overprint of carbonates, ocean and atmosphere pCO2 variations had to be reconstructed from δ13Corg values of marine organic matter. The δ13Corg signatures are affected by variable proportions of marine versus terrestrially derived organic matter and its state of preservation. Organic geochemical investigations (TOC [total organic carbon], C/N, lipid biomarkers) indicate the organic matter in the central Karoo Basin was primarily of algal origin. In agreement with element proxies, the varying δ13Corg values mirror shifts in pCO2, rather than variations of organic-matter type. A covariation trend between carbon isotope signatures of equatorial carbonates and δ13Corg values from the Karoo Basin argues against local forcing factors and instead implies a global climate-control mechanism. The 5–7 m.y. duration of a complete glacial cycle is not in tune with any known orbital frequency. Processes such as changes in equator-pole temperature gradients or newly developing atmosphere-ocean circulation pathways can be regarded as controlling factors.