The transition from fossil-based to bio-based materials requires in-depth environmental durability analysis for material engineering and construction applications. We report the hydrothermal aging and biodegradation effect on 6 types of compatibilized microcrystalline cellulose (MCC) and poly(butylene succinate) (PBS) composites. The prepared highly loaded systems with 70 wt% of MCC showed a strong positive impact on the composites’ mechanical and thermomechanical properties concerning applied modifications. MCC was modified with different coupling agents, namely polyhydroxy amides (PHA), alkyl ester (EST), (3-Aminopropyl)trimethoxysilane (APTMS), maleic acid anhydride, and polymeric diphenylmethane diisocyanate (PMDI). In addition, cross-linking agent carbodiimide (CDI) was used as an alternative to MCC modification. Modification of MCC compared to unmodified composite induced the enhanced rigidity, creep properties, and thermal stability of the materials due to the cross-linking in the interface by proposed chemical treatment. PMDI and CDI chemical modification resulted in the highest elastic modulus while keeping high strength values. A significant 2.5-fold reduction of the coefficient of linear thermal expansion and decreased thermal strains for modified biocomposites were obtained. Due to the hydrophilic nature of MCC, the hydrothermal aging of the composites revealed a dramatic decrease in the elastic modulus and strength characteristics compared to neat PBS. The hydrophilicity depends on the applied surface modification as indicated by contact angle measurements and water absorption and swelling tests. EST facilitated water wetting and enhanced water penetration, and reduced material biodegradation to 30 days, a 2.5-fold improvement compared to the neat PBS polymer. In contrast, PHA, APTMS, PMDI, and CDI improved biocomposites durability while suppressing biodegradation. The obtained results could be useful for selecting an optimal MCC surface modification route to design novel and perspective biocomposites with tailored durability and biodegradation and to replace polyolefin composites for wood polymer composite applications.