Regarding the reverse process of materials growth, etching has been widely concerned to indirectly probe the growth kinetics, offering an avenue in governing the growth of two-dimensional (2D) materials. In this work, interface-driven anisotropic etching mode is demonstrated for the first time to be generally applied to 2D heterostructures. It is shown that the typical in-plane graphene and hexagonal boron nitride (h-BN) heterostructures follow a multi-stage etching behavior initiated first along the interfacial region between the two materials and then along edges of neighboring h-BN flakes and finally along central edges of h-BN. By accurately tuning etching conditions in the chemical vapor deposition process, series of etched 2D heterostructure patterns are controllably produced. Furthermore, scaled formation of graphene and h-BN heterostructures arrays has been realized with full assist of as-proposed etching mechanism, offering a direct top-down method to make 2D orientated heterostructures with order and complexity. Detection of interface-driven multi-staged anisotropic etching mode will shed light on understanding growth mechanism and further expanding wide applications of 2D heterostructures.