Ti-6Al-4V titanium is considered a difficult-to-cut material used in critical applications in the aerospace industry requiring high reliability levels. An appropriate selection of cutting conditions can improve the machinability of this alloy and the surface integrity of the machined surface, including the generation of compressive residual stresses. In this paper, orthogonal cutting tests of Ti-6Al-4V titanium were performed using coated and uncoated tungsten carbide tools. Suitable design of experiments (DOE) was used to investigate the influence of the cutting conditions (cutting speed Vc, uncut chip thickness h, tool rake angle γn, and the cutting edge radius rn) on the forces, chip compression ratio, and residual stresses. Due to the time consumed and the high cost of the residual stress measurements, they were only measured for selected cutting conditions of the DOE. Then, the machine learning method based on mathematical regression analysis was applied to predict the residual stresses for other cutting conditions of the DOE. Finally, the optimal cutting conditions that minimize the machining outcomes were determined. The results showed that when increasing the compressive residual stresses at the machined surface by 40%, the rake angle should be increased from negative (−6°) to positive (5°), the cutting edge radius should be doubled (from 16 µm to 30 µm), and the cutting speed should be reduced by 67% (from 60 to 20 m/min).