Calcium oxide supported on ZrO2 is a highly active catalyst for base-catalyzed reactions such as aldol-type reactions and transesterification reactions. The role of key parameters during preparation, that is, impregnation versus precipitation, heat treatment, and metal oxide loading on the basicity and catalytic activity were investigated for CaO supported on ZrO2. An impregnation of 10 wt % CaO on monoclinic zirconia followed by heat treatment at 600 °C resulted in high activity for the self-condensation reaction of acetone. An evaluation of a series of CaO/ZrO2 samples with different loadings showed that the activity increased for impregnated amounts per gram catalyst of 0–10 wt % CaO, and at higher loading the activity decreased as a result of a decrease in dispersion. The number of strong base sites (calculated from CO2 desorbed at temperatures higher than 625 °C) correlated with the activity. For MgO, CaO, SrO, and BaO on zirconia the catalytic activity increased as the ionic radius of the metal cation increased, suggesting the impact of base strength on catalytic performance.