Van der Waals (vdW) heterojunctions, with their unique electronic and optoelectronic properties, have become promising candidates for photodetector applications. Amplifying the contribution of the depletion region in vdW heterojunction, which would enhance both of the collection efficiency and speed of the photogenerated carriers, presents an effective strategy for achieving high performance vdW heterojunction photodetectors. Herein, a fully depleted vdW heterojunction photodetector is built on two-dimensional (2D) semiconductor materials (GaTe and InSe) layered on a pattered bottom electrode in vertical structure, in which the generation and motion of carriers are exclusively achieved in the depletion region. Attributed to the intrinsic built-in electric field, the elimination of series resistance and the depletion region confinement of carriers, the as-fabricated photodetector exhibits prominent photovoltaic properties with a high open-circuit voltage of 0.465 V, as well as photoresponse characteristics with outstanding responsivity, detectivity and photoresponse speed of 63.7 A/W, 3.88 × 1013 Jones, and 32.7 μs respectively. The overall performance of this fully depleted GaTe/InSe vdW heterojunctions photodetectors are ranking high among the top level of 2D materials based photodetectors. It indicates the device architecture can provide new opportunities for the fabrication of high-performance photodetectors.