The Frome Embayment (Mesozoic) and Callabonna Sub-basin (Cenozoic) that overlie the Curnamona Province (Paleo-Mesoproterozoic) contain South Australia’s richest sandstone-hosted uranium deposits. This article considers organic matter (OM) as a key factor in explaining the region’s prospectivity for sandstone-hosted uranium. Sedimentary OM preserved in Cretaceous and Cenozoic sediments that overlie the Curnamona Province was examined and considered in terms of its potential to reduce and retain uranium. Shallow petroleum systems have generated hydrocarbons (mobile uranium reductant) within the Frome Embayment and Callabonna Sub-basin. In this area, the ‘oil window’ is demonstrably shallow due to elevated heat flow from buried radiogenic Proterozoic granite and elevated temperature gradients in the post-Cambrian succession arising from low thermal conductivities in the pre-Mesozoic sequence. Although aquifer temperature data are sparse, Great Artesian Basin (GAB) temperatures along the northern margin of the Curnamona Province stand out as being particularly high (52–63 ºC) and correspond to the early window for petroleum generation. The highest recorded GAB temperature is from the Woolatchie water bore at the northern extremity of the Poontana Trough where the Terrapinna Corridor separates the Mount Painter and Babbage Inliers. Here the Bulldog Shale is likely to be mature for liquid hydrocarbon generation. In addition, six organic facies are preserved within Mesozoic and Cenozoic strata overlying Curnamona Province basement rocks. These have varying capacity to generate hydrocarbons that in turn are capable of reducing and precipitating uranium from solution.