Lamina, a common lithologic unit in shale, is the smallest unit for organic–inorganic fluid–rock interactions. The effects of lamina-scale diagenetic processes are superimposed to exert on lithofacies-scale diagenetic sequences, which further impose on the entire diagenetic system of a shale reservoir. Organic acids from kerogen maturation are indispensable components in diagenetic reaction. However, previous studies mainly focused on low molecular weight (LMW) water soluble acids, few studies have paid attention to the role of high molecular weight (HMW) carboxylic acids dissolved in fluid–rock reactions. Herein, by taking the shale of the seventh member of the Upper Triassic Yanchang Formation in the Ordos Basin, China, as a case study, we investigate the mutual impacts between mineral alteration and HMW organic acid degradation. The characterization is carried out at two scales: lamina-scale (organic-rich clay-rich lamina and organic-lean silty lamina) and lithofacies-scale (shale and sandstone). Integrated analytical techniques (microdrill technique, thin section observation, X-ray diffraction, advanced mineral identification and characterization system, Rock-Eval pyrolysis, Fourier transform ion cyclotron resonance mass spectrometry) are performed. Results show that, in reservoirs of both silty lamina and sandstone, consumption of LMW aqueous acids through mineral transformation reactions promotes the forward evolution of HMW carboxylic acids in the bitumen phase toward decarboxylation or dehydration. During diagenesis, short chain fatty acids (SCFAs) are more easily broken down into small acids and, thus, more susceptible to be consumed. The lamina-scale reservoirs (silty lamina) have the privilege to receive abundant aqueous organic acids to maintain the micro-geochemical environment and progressively boost organic–inorganic fluid–rock interactions. The resultant dissolution pores not only accumulate plenty of bitumen but also an appreciable amount of bitumen dissolved acids. Because of the strong storage capacity of silty lamina within lithofacies-scale source rock (shale), fluids are less readily to expel out to lithofacies-scale reservoir (sandstone). As a result, the sandstone may not receive enough fluids from shale to maintain a consistent diagenetic environment, resulting in the observed discontinuous diagenesis of quartz precipitation transition to quartz dissolution.