Recent investigations on the fabrication of ultrathin silicon (Si) wafers using wire-electric discharge machining (wire-EDM) were observed to possess some inherent limitations. These include thermal damage (TD), kerf-loss (KL), and low slicing rate (SR), which constraints its industrial use. The extent of TD, KL, and SR largely depends on the process parameters such as open voltage (OV), servovoltage (SV), and pulse on-time (Ton). Therefore, optimizing the parameters that pertain to minimum TD and KL while maintaining a higher SR is the key to improvement in the fabrication of Si wafers using wire-EDM. Thus, this study is an effort to analyze and identify the optimal parameters that relate to the most effective Si slicing in wire-EDM. A central composite design (CCD)-based response surface methodology (RSM) was used for optimizing the process parameters. The capability to slice Si wafers in wire-EDM was observed to be influenced by the discharge energy, which significantly impacted the overall responses. The severities of TDs were observed to be mainly dominated by the variation in OV and Ton due to the diffusion of thermal energy into the workpiece, leading to melting and subsequent resolidification. For high productivity, the optimized parameters resulted in a SR of 0.72 mm/min, TD of 17.44 μm, and a kerf-loss of about 280 μm.