Resistance spot welding (RSW) is one of the most effective welding methods for titanium alloys, in particular Ti-6Al-4V. Ti-6Al-4V is one of the most used materials with its good ductility, high strength, weldability, corrosion resistance, and heat resistance. RSW and Ti-6Al-4V materials are often widely used in industrial manufacturing, particularly in automotive and aerospace industries. To understand the phenomenon of resistance spot weld quality, the physical and mechanical properties of Ti-6Al-4V spot weld are essential to be analyzed. In this study, an experiment was conducted using the Taguchi L9 method to find out the optimum level of the weld joint strength. The given optimum level sample was analyzed to study the most significant affecting RSW parameter, the failure mode, the weld nugget microstructure, and hardness values. The high heat input significantly affect the weld nugget temperature to reach and beyond the β-transus temperature. It led to an increase in the weld nugget diameter and the indentation depth. The expulsion appeared in the high heat input and decreased the weld nugget strength. It was caused by the molten material ejection in the fusion zone. The combination of high heat input and rapid air cooling at room temperature generated a martensite microstructure in the fusion zone. It increased the hardness, strength, and brittleness but decreased the ductility.