Joining titanium alloys by friction stir welding (FSW) is a multifarious process that involves thermal and mechanical phenomena at the weld interface. As such, the literature shows that there is a need for a welding fixture to constrain the workpieces firmly and to withstand the various forces and temperatures developed during the joining process. Therefore, in this research, a solemn attempt is made to conduct a series of pilot experiments for FSW of titanium sheets in a conventional vice setup, and the various defects and failures that arose during the processes were established. The welding fixture was designed considering the 3–2–1 principle of location for constraining the corresponding degrees of freedom and based on the defects and failures encountered in the pilot experiments. The selection of suitable fixture material was analyzed for three different materials using finite element analysis (FEA). After the selection of the suitable material from the analysis, the fixture was fabricated using various techniques and then heat-treated accordingly. The efficacy of the fabricated fixture was validated by experimental investigation by joining a titanium alloy. The validation results confirmed that a superior weld joint was obtained in comparison with the pilot experiments.