The plasma in contact with liquids has led to various novel applications such as plasma biomedicine, material synthesis, and so on. However, the phenomenon of evaporation under plasma treatment and its impact on plasma–liquid interactions has a limited understanding. In this study, the spatially and temporally resolved behavior of water vapor production and its induced influences on plasma properties and gaseous chemistry were studied in detail in an atmospheric pressure pin‐to‐water pulsed He discharge. Diagnostic methods such as laser‐induced fluorescence (LIF) and high‐resolution optical emission spectroscopy (OES) were applied to determine the water vapor and OH radical densities, as well as key plasma parameters such as the gas temperature and electron density. It shows that the physicochemical properties of plasma vary among different discharge regions due to evaporation behavior stimulated during the pulsed discharge‐on phase. In addition, using simulation based on the experimental data, the mechanisms of how water vapor affects the observed spatiotemporal behaviors of OH radicals in different discharge regions are understood. Compared to the pin‐anode and liquid‐cathode sheath regions, proper electron parameters such as density and temperature, as well as water vapor density in the plasma‐positive column, significantly enhance the production of reactive OH radical through the dominant path of electron‐stimulated H2O dissociation. However, higher levels of electron parameters in the intense discharge region near the positive‐pin boundary enhance OH dissociation and finally result in the hollow distribution of OH density. From the global kinetic plasma simulation, the production of reactive hydroxide species playing key roles in plasma medicine treatments, such as O, H, HO2, H2O2, and hydrated ions including H+(H2O)4 and H+(H2O)5, are promoted noticeably as a result of the enhanced water evaporation process.