Inconel 718 alloy is difficult to machine using conventional methods due to its physical properties. Thereby, additive manufacturing (AM) of IN718 components with near-net shapes has been extensively studied. Even though AM processes provide shape and size accuracy, there is still the need for the machining of the AM-processed components to achieve the final shape of a component. Laser powder bed fusion (LPBF) has been successfully utilized to fabricate near-net shape IN718 components; moreover, the microstructure of LPBF-IN718 was unique owing to the AM processing, resulting in differences in grain size, grain boundary characteristics, and grain orientations. Furthermore, these microstructural characteristics are expected to alter the machining performance of IN718. Therefore, this study investigated the wire electro-discharge machining (WEDM) performance of LPBF-718 samples compared to wrought IN718 while focusing on the unique microstructure characteristics of LPBF-IN718 samples (lamella, single-crystal, ploy-crystal). Three different cutting strategies (rough, semi-finish, and finish) were implemented to understand the performance of the multi-pass cutting phenomenon and its effect on the surface of IN718. For all samples, rough (single pass) cutting displayed high roughness, while finish (three passes) cutting exhibited good surface quality. Compositional analyses on the machined surface showed debris formation including Zn and Cu-containing recast material, indicating wire erosion. The surface of single-crystal LPBF-IN718 after the WEDM process was smooth owing to its large grain size and less amount of grain boundary, resulting in slow cutting speed but a good surface finish. Thus, this study, for the first time, investigated the effect of unique microstructural characteristics of LPBF-fabricated IN718 on WEDM performance and machined surface quality.