Organic-mineral interactions are pervasive in sedimentary environments; however, the extent of these interactions is not constant and has a significant impact on organic carbon (OC) occurrence and transformation. To understand the evolution of organic-mineral interactions and the implications for OC occurrence and transformation in fine-grained sediments, several shale samples were selected and subjected to physical and chemical sequential treatments. The samples were subjected to pyrolysis, Fourier transform infrared spectrophotometry (FTIR), and adsorption measurements to determine the organic parameters and the mineral surface area (MSA) of the shale samples. The results show that the organic fractions derived from sequential treatments have varying pyrolysis and FTIR characteristics. The correlation between the total OC content and MSA is positive, but it is split according to organic fractions with different attributes. Correlations between the different organic fractions and MSA indicate that the organic matter in shale is mainly adsorbed on mineral surfaces, while a certain portion of organic matter occurs in the pores and is adsorbed on the organic-mineral aggregates, suggesting variable interactions between the organic fractions with different attributes and minerals. From the pyrolysis and FTIR analysis, the organic fractions of different occurrence sites vary in their OC proportion, proclivity to form organic functional groups, and hydrocarbon generation potential. With increasing burial depth, the MSA and hydrogen index as well as OC loading per unit MSA are reduced, and the OC proportions of organic fractions with different attributes have regular trends. These observations indicate that the extent of organic-mineral interactions that can stabilize organic matter gradually decreases, resulting in transformation of the tightly mineral-combined OC into free OC. Our work reveals the heterogeneity in organic matter occurrence and the effect of the evolution of the organic-mineral interactions on OC occurrence and transformation, which is significant in the global carbon cycle and in petroleum systems.