Resistive switching memories based on the formation and dissolution of a metal filament in a simple metal/oxide/metal structure are attractive because of their potential high scalability, low-power consumption, and ease of operation. From the standpoint of the operation mechanism, these types of memory devices are referred to as gapless-type atomic switches or electrochemical metallization cells. It is well known that oxide materials can absorb moisture from the ambient air, which causes shifts in the characteristics of metal-oxide-semiconductor devices. However, the role of ambient moisture on the operation of oxide-based atomic switches has not yet been clarified. In this work, current–voltage measurements were performed as a function of ambient water vapor pressure and temperature to reveal the effect of moisture on the switching behavior of Cu/oxide/Pt atomic switches using different oxide materials. The main findings are: i) the ionization of Cu at the anode interface is likely to be attributed to chemical oxidation via residual water in the oxide layer, ii) Cu ions migrate along grain boundaries in the oxide layer, where a hydrogen-bond network might be formed by moisture absorption, and iii) the stability of residual water has an impact on the ionization and migration processes and plays a major role in determining the operation voltages. These findings will be important in the microscopic understanding of the switching behavior of oxide-based atomic switches and electrochemical metallization cells.