Direct Z-scheme heterojunction can effectively enhance the photocatalytic activity due to its low carrier recombination rate and high redox ability. In this study, a 2D/2D ZnO/ZnxCd1-xS single crystal nanosheet heterojunction is synthesized in situ by topotactic sulfurization/oxidization pyrolysis of Zn/Cd/Al layer double hydroxides (LDHs). Its unique structure provides not only numerous intimate interfaces but also a direct Z-scheme junction. The in situ topotactic fabrication of ZnO by the oxidation process causes some Zn ions to dissolve out from the Zn(0.67)Cd(0.3)3S solid solution nanosheets with increase in annealing temperature and time. The longer the time for oxidation, the more ZnO is obtained. The formation of ZnO yields 2D/2D ZnO/ZnxCd1-xS single crystal nanosheet heterojunction, which increases the visible light absorption and boosts the separation of photogenerated carriers. The ZnO/ZnxCd1-xS-4 single crystal nanosheet heterojunction presents the highest photocatalytic activity under visible light irradiation (38.93 mmol h(-1) g(-1)), which is nearly 16.93 times higher than that of Zn0.67Cd0.33S-300, and an external quantum efficiency of 40.97% at = 420 nm. The proposed synthetic route for the construction of 2D/2D ZnO/ZnxCd1-xS single crystal nanosheet provides a direct Z-scheme structure with highly efficient photocatalytic hydrogen evolution activity.