Aptian to Campanian sediments from the Western offshore to Central Orange Basin were studied by integrating molecular geochemistry, inorganic and isotopic studies to recognize their geochemical characteristics via the reconstruction of the Orange basin’s paleoweathering, paleosalinity, paleovegetation, paleoclimate, and tectonic records. Molecular analyses of both aliphatic and aromatic compounds reveal an input dominantly from a marine source. The source rocks accumulated in a reduced, anoxic, saline water column. Based on various biomarker proxies and vitrinite reflectance data, some samples are thermally mature to produce petroleum, while others are not. According to the V/Ni ratio, samples from the Orange Basin in South Africa are mainly anoxic, with only a few samples ranging from suboxic to anoxic. This is congruent with biomarker and isotope analyses that further indicate the presence of marine-derived source rocks with some terrestrial remains generating hydrocarbons. The investigated sediments are made up of intermediate igneous rocks that have undergone moderate chemical weathering. Geochemical figures on tectonic setting discriminant function diagrams revealed a continental rift of passive margin settings. As a result, the extrapolated crustal processes are directly analogous to the genesis and evolution of the Orange Basin, demonstrating Gondwana’s breaking up and the opening of the Atlantic Ocean Margin.