Ketonization reactions provide a feasible approach to remove oxygen and increase carbon chain length for conversion of biomass derived carboxylic acids. However, the reaction suffers from fast catalyst deactivation and low ketone selectivity. In this work, Lewis acidic heteroatom Ti-, Zr-, Ce-, and Sn-Beta zeolites were prepared using a twostep post-synthesis method and applied in vapor phase ketonization of propionic acid at 350 °C. Among these zeolites, Zr-Beta shows both the highest activity and selectivity. Characterizations indicate that Zr prefers the vacant tetrahedral site when the Zr content is < 7%, corresponding to the maximal fraction of vacant sites produced from dealumination of the parent H-Beta with a Si/Al ratio of 19. Extraframework Zr may also form at a Zr content ≥ 7%. The tetrahedrally coordinated framework Zr species (mainly in the structure of open sites) show Lewis acidic characteristic, and their density can be linearly correlated with the ketonization activity, indicating that these sites are active sites for ketonization. In contrast to rapid deactivation of H-Beta, the 7% Zr-Beta is stable for ketonization over 60 h, maintaining a conversion of ∼50% and a 3-pentanone selectivity > 96% at a space time of 2 h. The amount of coke deposition on Zr-Beta is about 1/3 of that on H-Beta, and the structure of Zr-Beta is preserved after 60 h of reaction. The results of this work indicate that Zr-Beta zeolite is a promising catalyst for ketonization with good stability and high selectivity toward ketone.