A three-dimensional heat transfer and material flow-based model using experimentally measured thermo-physical properties has been developed for friction stir welding (FSW) of Cu-0.8Cr-0.1Zr alloy. CuCrZr alloy is a precipitation-hardened copper alloy with good electrical and thermal conductivity and moderate strength at elevated temperatures. The temperature-dependent specific heat, thermal conductivity, and yield strength of the alloy were determined experimentally to develop a reliable and accurate numerical model. The results from numerical model were validated by performing suitable experiments for numerous tool rotational speeds and welding speeds during joining of 3-mm-thick CuCrZr alloy on a dedicated FSW machine. The temperature evolution across the welds was measured using thermocouples. The results from the developed numerical model were validated by comparing it with the measured weld thermal cycles, peak temperatures, and thermo-mechanically-affected zone (TMAZ) for various welds. Validation was also supported with microstructural evidences from the weld nugget zone and TMAZ. The developed model showed the capability to simulate FSW of CuCrZr alloy and predict the important results with reasonably good accuracy.