The largest terrestrial organic carbon pool, carbon in soils, is regulated by the intricate connection between plant carbon inputs, microbial activity, and soil matrix. This is manifested by how microorganisms, the key players in transforming plant-derived carbon into soil organic carbon, are controlled by the physical arrangement of organic and inorganic soil particles. We studied the role of soil structure on the fate of litter-derived organic matter and we propose that the persistence of soil carbon pools is directly determined at plant–soil interfaces. We show that while microbial activity and fungal growth is controlled by soil structure, occlusion of organic matter into aggregates and formation of organo-mineral associations occur in concert on litter surfaces regardless of soil structure. These two mechanisms—the two most prominent processes contributing to the persistence of organic matter—occur directly at fresh litter that constitutes a key nucleus in the build-up of soil carbon persistence.