Copper clad polyimide is becoming a significant raw material for the manufacturing of special circuits such as antennas. Micro-milling, which provides a direct and flexible fabrication method in three-dimensional product machining, has replaced traditional processing methods such as photolithography. However, severe burr problem which leads to serious power loss due to the skin effect is encountered because of the selection of improper machining strategies and parameters. In this study, the influence of machining strategy on burr formation is investigated at first. Then, the formation mechanism for different kinds of burrs in micro-milling of copper clad polyimide is analyzed. Furthermore, the burr height prediction model is established, and the optimized processing parameters are obtained through response surface methodology, the predicted burr height is 12 µm. At last, a verification experiment is conducted with the optimized processing parameters. The machining result shows that the optimized parameter combination contains spindle speed of 36,110 r/min, feed per tooth of 0.70 µm/z and tool diameter of 200 µm. The average burr height for verification test is 13.9 µm. Because of the instability of copper layer on copper clad polyimide, the actual burr height is slightly larger than theoretical prediction. The error between predicted value and experiment value is 15.8%. What is noticeable is that before optimization, the burr height is up to 100 µm, while after optimization, it reduces to 13.9 µm which is reduced by 86.1%. The achievements in this study are of great significance for optimizing machining parameters and improving machining quality and efficiency of copper clad polyimide, especially in antennas field.