Abstract A novel Sc2O3–SiO2 catalyst was explored and evaluated for the upgrade of ethanol and acetaldehyde to butadiene. Notably, the Sc2O3–SiO2 catalyst with a Sc/Si molar ratio of 0.06 demonstrated exceptional performance, exhibiting the highest selectivity of 81.7% for butadiene alongside a selectivity of 10.2% for butanol. When the Sc/Si ratio was increased to 0.3, the butanol selectivity increased to 30.0%. To elucidate the underlying factors governing these results, detailed characterizations of the catalysts structure and acidic–basic properties were conducted for the Sc2O3–SiO2 materials. The analyses revealed that the higher percentage of strong acidic sites in total acidic sites was conducive to higher butadiene yield, while the increased density of strong basic sites correlated with higher butanol selectivity.