Fabrication of homogeneous hydrophobic polymer/cellulose nanocrystals (CNCs) nanocomposites with high mechanical reinforcement is a tough issue owing to the poor interfacial interactions between the two components and the aggregation of CNCs in hydrophobic matrices. In this study, the polybutadiene (PB) nanocomposites reinforced with cotton-derived CNCs were prepared through a host-guest inclusion complex assisted approach. In the system the pendent guest adamantane moieties of PB reacted with beta-cyclodextrins (beta CDs) to form inclusion complexes, which acted as competitive binding sites to the CNCs via hydrogen bonds, allowing the CNCs to disperse homogeneously in the matrix. Dynamic mechanical analysis and tensile testing studies of the nanocomposites revealed that the incorporation of CNCs into the polymer matrix significantly improved the mechanical properties. For the nanocomposites with 10 wt % beta CDs and 15 wt % CNCs, the storage modulus, Young's modulus, and tensile strength were enhanced by about an order of magnitude compared to neat PB. The increase in the beta CD and/or CNC contents led to a shifting of the tan delta peak of the nanocomposite to higher temperatures, suggesting the presence of filler-polymer interactions. Moreover, scanning electron and polarized optical microscopy analyses revealed that in the matrix the individual CNCs aligned in parallel and longitudinal directions to form long and entangled assemblies. The reinforcement could be attributed to the filler-filler and filler-matrix interactions which consequently led to the stress transfer between polymer and CNCs in the system.