Aircraft engine fan blades are notably designed to withstand impact loading involving large deformation, high strain rate, non-proportional loading paths and self-heating. Due to their high strength-to-weight ratio and good toughness, Ti–6Al–4V titanium alloys are promising candidates for the blades leading edge. An extensive experimental campaign on a Ti–6Al–4V titanium alloy provided in the form of cold rolled plates has been carried out. The thermo-mechanical characterization consisted in tension, compression and shear tests performed at various strain rates and temperatures, and under monotonic as well as alternate loading paths. A constitutive model has been accordingly developed accounting for the combined effect of plastic orthotropy and tension/compression asymmetry, nonlinear isotropic and kinematic strain hardening, strain rate hardening, and thermal softening. The constitutive model has been implemented as a user material subroutine into the commercial finite element computation code LS-DYNA. The performances of the model have been estimated by conducting numerical simulations considering a volume element under various loading paths as well as the specimens used for the experimental campaign.