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 hBN. 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.