Ketonization can efficiently convert carboxylic acids into ketones, promising in bio-oil upgrading. For economic-sustainable bio-refining, Ca/Zn/AlOx (CZA) metal oxides with various Ca/Zn/Al ratios have been prepared by the low-cost and natural abundant metals and are applied in the process here. Mechanistic study on the ketonization of acetic acid revealed the reaction pathways strongly depends on "composition-structure-function" correlation of the Ca/Zn/AlOx catalysts. The reaction is mainly performed on strong base sites (e.g. CaO and ZnO) via thermal decomposition of carboxylates at high temperature (>= 375 degrees C), but depends on acid-base pairs (e.g. amorphous calcium aluminates) significantly at low temperature (<= 350 degrees C). CZA(331) (Ca/Zn/Al = 3/3/1) obtained the highest acetone yield of 97.1% at 425 degrees C hitherto and retained for over 100 h with simple regeneration process. Adding major bio-oil model compounds (e.g. phenol) into the reaction mixture has minor effect on the CZA catalysts. Therefore, current highly active and stable CZA catalysts are promising in boosting the efficiency and economy of bio-oil upgrading process in future.