Influence of nanoparticle (NP) spatial organization on relaxation and mechanical properties of polymer nanocomposites (PNCs) was investigated. For the first time, the properties of PNCs with various nanostructures at the constant chemical composition were related to their experimentally determined structural parameters-effective interfacial surface and interparticle distance. Segmental scale reinforcement active below and above glass transition was attributed to the immobilization and frustration of polymer segments caused by attractive polymer-particle interactions. A novel reinforcing mechanism of chain bound clusters related to their internal structure was revealed while negligible reinforcement from NP-NP interactions of contact aggregates was found. The mechanical response of PNCs was correlated with appropriate relaxation properties. It provided the first experimental proof that deformation yielding dynamics of PNCs is controlled by glass transition segmental mobility. Main features of various NP spatial organizations were characterized. Chain bound clusters showed the most significant reinforcement above the glass transition temperature (T-g). Moreover, the hierarchical nature of chain bound clusters caused broadening of the ductile response compared to other nanostructures and also to the neat matrix. The most pronounced enhancement of elastic modulus, yield stress, and creep durability was found for individually dispersed NPs. The acquired nanostructure-property relationships will provide a foundation for the future design of hierarchic and multidomain nanocomposites.