The ketonic decarboxylation of carboxylic acids has been carried out experimentally and studied theoretically by DFT calculations. In the experiments, monoclinic zirconia was identified as a good catalyst, giving high activity and high selectivity when compared with other potential catalysts, such as silica, alumina, or ceria. It was also shown that it could be used for a wide range of substrates, namely, for carboxylic acids with two to eighteen carbon atoms. The reaction mechanism for the ketonic decarboxylation of acetic acid over monoclinic zirconia was investigated by using a periodic DFT slab model. A reaction pathway with the formation of a β-keto acid intermediate was considered, as well as a concerted mechanism, involving simultaneous carbon–carbon bond formation and carbon dioxide elimination. DFT results showed that the mechanism with the β-keto acid was the kinetically favored one and this was further supported by an experiment employing a mixture of isomeric (linear and branched) pentanoic acids.