Three-dimensional atom-probe tomography and first-principles calculation combined with density functional theory were used to study the effect of the co-segregation of different elements formed during the solidification process of S32205 duplex stainless steel on the Cr-depleted zone at the interface between ferrite and austenite. It was found that the co-segregation of different elements formed during the solidification process of duplex stainless steel can also form Cr-depleted zone at the interface between ferrite and austenite. Moreover, Mo, Si, B, C and P atoms promote co-segregation with Cr atoms, which promotes the formation of Cr-depleted zone at the interface between ferrite and austenite in duplex stainless steel. Mo and Si strongly promote the segregation of Cr at the interface between ferrite and austenite, thereby promoting the formation of Cr-depleted zone. B, C and P elements also promote the segregation of Cr element at the interface between ferrite and austenite and the formation of Cr-depleted zone, but their effect is weaker than that of Mo and Si elements. These conclusions provide a new theoretical basis for improving the intergranular corrosion performance of duplex stainless steel.