Single-atom catalysts have emerged as a new frontier in catalysis science. However, their applications are still limited to small molecule activations in the gas phase, the classic organic transformations catalyzed by single-atom catalysts are still rare. Here, we report the use of a single-atom Pd catalyst for the classic Suzuki–Miyaura carbon–carbon coupling reaction under phosphine-free and open-air conditions at room temperature. The single-atom Pd catalyst is prepared through anchoring Pd on bimetal oxides (Pd-ZnO-ZrO2). The significant synergetic effect of ZnO and ZrO2 is observed. The catalyst exhibits high activity and tolerance of a wide scope of substrates. Characterization demonstrates that Pd single atoms are coordinated with two oxygen atoms in Pd-ZnO-ZrO2 catalyst. The catalyst can be fabricated on a multi-gram scale using a simple in situ co-precipitation method, which endows this catalytic system with great potential in practical applications.