An interdisciplinary study was carried out to unravel organic–inorganic interactions caused by the radiogenic decay of uranium in the immature organic-rich Alum Shale (Middle Cambrian-Lower Ordovician). Based on pyrolysis experiments, uranium content is positively correlated with the gas-oil ratios and the aromaticities of both the free hydrocarbons residing in the rock and the pyrolysis products from its kerogen, indicating that irradiation has had a strong influence on organic matter composition overall and hence on petroleum potential. The Fourier Transform Ion Cyclotron Resonance mass spectrometry data reveal that macro-molecules in the uranium-rich Alum Shale samples are less alkylated than less irradiated counterparts, providing further evidence for structural alteration by α-particle bombardment. In addition, oxygen containing-compounds are enriched in the uranium-rich samples but are not easily degradable into low-molecular-weight products due to irradiation-induced crosslinking. Irradiation has induced changes in organic matter composition throughout the shale's entire ca. 500 Ma history, irrespective of thermal history. This factor has to be taken into account when reconstructing petroleum generation history. The Alum Shale's kerogen underwent catagenesis in the main petroleum kitchen area 420–340 Ma bp. Our calculations suggest the kerogen was much more aliphatic and oil-prone after deposition than that after extensive exposure to radiation. In addition, the gas sorption capacity of the organic matter in the Alum Shale can be assumed to have been less developed during Palaeozoic times, in contrast to results gained by sorption experiments performed at the present day, for the same reason. The kerogen reconstruction method developed here precludes overestimations of gas generation and gas retention in the Alum Shale by taking irradiation exposure into account and can thus significantly mitigate charge risk when applied in the explorations for both conventional and unconventional hydrocarbons.