This study develops a combined numerical and experimental approach to get deeper insights into chip formation mechanism for high-speed machining of titanium alloy Ti6Al4V. The numerical investigation of high-speed machining is implemented with the aid of finite element analysis software Abaqus/Explicit, in which the Johnson-Cook (JC) fracture model with an energy-based ductile failure criterion is adopted. Meanwhile, the experiments of high-speed orthogonal cutting are carried out to validate the numerical results. The cutting speeds are selected ranging from 50 to 3,000 m/min, and the uncut chip thickness is fixed at 0.1 mm. The variables investigated include the serrated degree and serrated frequency of chips in addition to the cutting force. The results show that both the serrated degree and serrated frequency have positive correlations with the cutting speed. An important regularity for the transformation of chip morphology from serrated to unit at a critical cutting speed has been achieved, and the critical value for Ti6Al4V is about 2,500 m/min. The research also finds that the cutting force decreases with the increasing cutting speed, while its fluctuant frequency and amplitude increase sharply. Furthermore, the influences of JC fracture constants (the five constants in JC fracture model) on chip formation are investigated based on the finite element method, which is the main original and innovative highlight of this study. The shear localization sensitivity is firstly proposed to describe the influences of JC fracture constants on the chip formation process. When the JC fracture constants decrease, the shear localization sensitivity is positive which means that the serrated degree increases and vice versa. The sensitivity analyses indicate that the influences of initial failure strain D 1 and exponential factor of stress triaxiality D 2 on chip formation process are more conspicuous than the rest three ones. This paper is enticing from both the engineering and the analytical perspectives aimed at predicting the evolution of serrated chip formation and chip morphology transformation in metal cutting process.