Methylammonium lead halide perovskites have gained a lot of attention because of their remarkable physical properties and potential for numerous (opto)electronic applications. Here, high-performance photodetectors based on CH3NH3PbI3 (MAPbI3)/CdS heterostructures are demonstrated. The resulting self-powered MAPbI3/CdS photodetectors show excellent operating characteristics including a maximum detectivity of 2.3 × 1011 Jones with a responsivity of 0.43 A/W measured at 730 nm. A temporal response time of less than 14 ms was achieved. The mechanisms of charge separation and transport at the interface of the MAPbI3/CdS junction were investigated via conductive atomic force microscopy (AFM) and photoconductive AFM. Obtained results show that grain boundaries exhibit higher photocurrent than flat regions of the top perovskite layer, which indicates that excitons preferentially separate at the grain boundaries of the perovskite thin film, that is, at the edges of the MAPbI3 crystals. The study of the photoelectric mechanism at the nanoscale suggests the device performance could potentially be fine-tuned through grain boundary engineering, which provides essential insights for the fabrication of the high-performance photodetector. The demonstrated self-powered photodetector is promising for numerous applications in low-energy consumption optoelectronic devices.