Zirconium is used commercially for nuclear power generation and for increasing electricity output. However, its poor thermal conductivity may result in buildup of residual stress during machining, thereby affecting its machinability. This study investigates the temperature variation of zirconium alloy using Response Surface Methodology (RSM). Three process parameters were used during the milling operation: depth of cut (0.1-0.35 mm), feed per tooth (0.1 -0.25 mm), and cutting speed (50-200 m/min). The experimental matrix generated by RSM was validated via physical machining taking cutting temperature as the measured response. The milling operations were conducted using a DMU80 monoBLOCK DECKEL MAHO Computer Numerical Control (CNC) milling with the aid of Polycrystalline Diamond Tool (PCD) of 50 mm × 100 mm, diameter of 10 mm, with 12o positive rake angle. Findings shows that the optimal values of the process parameters that gave moderate cutting temperature (100.8 oC) were: depth of cut (0.225 mm); feed per tooth (0.175 mm) and speed of cut (125 m/min). This results suggest that there might be a tradeoff. Furthermore, the statistical analysis of the developed predictive model gave a P-value of 0.0021 (less than 0.05) and F-value of 6.68 which indicate the developed model is significant. Hence, this study may assist machinists in achieving the effective machining of zirconium alloys and prediction of cutting temperature.