3-hydroxybutyraldehyde (3-HBA) is mainly employed to synthesize 1,3-BDO (1,3-butanediol), which is one of the most important components in cosmetics moisturizers. In this study, a series of composite oxide catalysts were prepared by bringing alkaline earth metal Ca and rare earth metal La to the composite oxide MgO/Al2O3, which were made through the co-precipitation method. These catalysts were applied in the synthesis of 3-HBA through acetaldehyde (AcH) condensation. The structure, texture, and acidic properties of these catalysts were characterized using various characterization methods, and the effects of catalyst composition, reaction temperature, reaction pressure, and residence time on the conversion of AcH were investigated as well. The results showed that the introduction of Ca and La weakened the acidic property and enhanced the basic property, which favored the AcH condensation to synthesize 3-HBA. At a temperature of 20 °C, pressure of 200 kPa, and residence time of 70 min, 0.5%La-2.3%Ca-2MgO/Al2O3 exhibited a better catalytic activity, and the conversion of AcH reached 95.89%. The selectivity and yield of 3-HBA were 92.08% and 88.30%, respectively. The stability test indicated that the high AcH conversion could be maintained for 5 h.