The invention belongs to the field of precision measurement, and relates to a vision sensing based AFM (Automatic Force Microscope) system mechanical drift compensation method. The method is characterized in that an AFM system drift compensation algorithm is built on the basis of positioning the position of microspheres under a microscope through image processing. Due to influences imposed on an AFM system by factors such as mechanical vibration and noise interference, the variation in distance between a cantilever tail end microsphere and a sample surface microsphere is accumulation of the drift of the AFM system, and driver voltage of a platform at which the microspheres are located is adjusted according to the measured distance variation, so that the distance between the cantilever tail end microsphere and the sample surface microsphere is enabled to be kept as a constant, and thus compensation for the drift amount of the AFM system is realized. Compared with an existing AFM system drift compensation method, the method provided by the invention has the advantages of ability of not changing hardware of the AFM system and non-contact measurement, and can compensate the drift of the AFM system in real time.