For the first time, an electrochemical mechanism of oxidative dissolution of silver nanoparticles in aqueous solutions is suggested and substantiated. The dissolution is caused by the occurrence of two interrelated electrochemical processes: (1) silver oxidation on a microanode and (2) oxygen reduction on a microcathode. According to the suggested model, the standard electrode potential of a nanoparticle decreases with a decrease in its size, which leads to an increase in the electromotive force of the oxidative dissolution of silver. A proportional dependence of the solubility of nanoparticles on their standard potential is revealed. An empirical equation is derived that relates the solubility of AgNPs to their electrode potential and size. In the course of oxidation, silver nanoparticles undergo aggregation with a gradual increase in the potential to the value characteristic of the bulk metal. This leads to the deceleration and practical cessation of the dissolution.