Volcano curves have proven to be particularly useful in new catalyst design in the field of heterogeneous catalysis. On the other hand, the further enhancement of the performance of the optimal catalyst for a given reaction is inherently limited by the Sabatier principle. In this work, microkinetic analysis has been carried out to examine the adsorption and catalytic behaviors of single-atom-doped Ga 2 O 3 catalysts in propane dehydrogenation (PDH), which shows that the volcano-shaped activity plot can be broken through by Lewis acid–base interactions, making it possible to achieve better catalytic performance than that of the most active catalyst lying near the summit of the volcano. The reasoning behind this finding is that the presence of the Lewis acid–base interaction over metal-oxide surfaces may strengthen the coadsorption of a pair of amphoteric species at the M–O site, resulting in distinctly different chemisorption energy and transition state energy scaling relations. As a result, the formation energies of H&H coadsorption at the M–O site and H adsorption on top of O are identified as two different reactivity descriptors in the presence and absence of the Lewis acid–base interaction, respectively, with the resulting activity plots exhibiting a straight-line and a volcano-curve pattern. Further experiments verify that the theoretically predicted catalyst candidate Ir 1 –Ga 2 O 3 is more effective than the previously reported trace-Pt-promoted Ga 2 O 3 catalyst, which opens up a new way to the rational design of metal-oxide catalysts for the PDH process.