Arsenopyrite (FeAsS) is one of the sulfide minerals of seafloor massive sulfide deposits. The presence of sodium chloride and high-temperature and high-pressure (HTHP) geological conditions seriously affect the process of arsenopyrite weathering. However, electrochemical oxidative dissolution has never been considered in the context of seafloors, though it has already been shown to increase dissolution significantly in terrestrial deposits. In this work, in situ electrochemical techniques and surface analysis were used to investigate the behaviors of oxidative arsenopyrite dissolution in different concentrations of NaCl at temperatures ranging from 280 to 360 °C and pressures ranging from 12.0 to 20.0 MPa. In the initial stage, arsenopyrite was oxidized to S⁰, As(III), and Fe(II). The S⁰ and As(III) were ultimately converted into SO₄²⁻ and AsO₄³⁻ and entered the solution. The Fe(II) was converted into α-FeOOH, γ-FeOOH, and Fe₂O₃ as a passivation film. The presence of Cl⁻ ions promoted the oxidative dissolution of arsenopyrite without changing its oxidation mechanism. Higher temperatures or greater pressures promoted the oxidative dissolution of arsenopyrite by enhancing charge migration and ion diffusion. Under the experimental HTHP conditions, the oxidative arsenopyrite dissolution rate constant was 8.0 × 10^–5 mol∙m⁻²∙s⁻¹. This work expands the understanding of the geochemical cycles of Fe, As and S and provides an experimental basis for the formation of secondary minerals from arsenopyrite weathering under the hydrothermal solution conditions of the seafloor.