Polytetrafluoroethylene (PTFE) is one of the most used materials for sealing applications. Despite remarkable properties, PTFE has poor wear resistance which causes leakage problems during sealing. Studies have shown that the most important factor for improving the sealing properties of the PTFE matrix is adding suitable fillers as the reinforcing phase. Therefore, the design and fabrication of the PTFE-based composite with new reinforcements is a highly demanded research to enhance sealing properties. In this investigation, atomized powder of the Inconel 625 alloy which is a Nickel-based superalloy was used as a reinforcing phase to fabricate the PTFE-based composite. The effect of different weight percentages of the Inconel 625 was investigated on the wear, corrosion, and leak rate properties of the PTFE-based composites. The result showed that the predominant abrasion mechanism of the PTFE/Inconel 625 composite is the usually adhesive type with proper corrosion resistance against hydrochloric acid, sulfuric acid, and hydrogen fluoride. Among the fabricated composites, the mixture of 50 % Inconel 625 alloy and 50 % PTFE exhibited the best combination of properties with a leak rate of approximately 10−9 mbar L s−1. Besides, the molecular dynamics (MD) simulation was applied to study the interface of the PTFE and the Inconel 625 alloy particles, the wear, and the permeability behavior of the composites. Based on the obtained results, the novel PTFE composite can be applied as a sealing application for industrial purposes.