Utilization of biomass-derived monomeric building blocks to formulate polyurethane materials can significantly reduce the complexity of the target network generated by the uncertainty of raw biomass. Herein, in this study, four cleavable vanillin-based polyols were prepared from vanillin and two sustainable feedstocks, 2,5-furandicarboxylic acid (FDCA) and terephthalic acid (TPA), followed by the cross-linking with two different isocyanates. The resulting polyurethane samples exhibited reasonable mechanical strength, thermostability, and solvent resistance. Of great importance is that the inherent ester bonds in the network endowed these samples with outstanding degradability, evidenced by the impressive weight loss in aqueous NaOH solution at room temperature (weight loss of up to ∼35% after 24 h). Notably, the glass-transition temperature (Tg) of these materials can be tunable by using different isocyanates, ranging from 26 to 101 °C in this work, which could potentially meet application requirements in different fields. This study provides an encouraging first step in formulating mechanically strong, thermally stable, and easily degradable polyurethane samples that are potentially useful in practical applications (i.e., coating and packaging).