The thiolate-catalyzed Tishchenko reaction has shown high chemoselectivity for the formation of double aromatic-substituted esters. In the present study, the detailed reaction mechanism and, in particular, the origin of the observed high chemoselectivity, have been studied with DFT calculations. The catalytic cycle mainly consisted of three steps: 1,2-addition, hydride transfer, and acyl transfer steps. The calculation results reproduce the experimental observations that 4-chlorobenzaldehyde acts as the hydrogen donor (carbonyl part in the ester product), while 2-methoxybenzaldehyde acts as the hydrogen acceptor (alcohol part in the product). The two main factors are responsible for such chemoselectivity: 1)in the rate-determining hydride transfer step, the para-chloride substituent facilitates the hydride-donating process by weakening the steric hindrance, and 2)the ortho-methoxy substituent facilitates the hydride-accepting process by stabilizing the magnesium center (by compensating for the electron deficiency).