This study primarily aims to develop a robust modeling approach to capture the complex material behavior of CP-Ti, appeared by high anisotropy, differential hardening due to anisotropy evolution, and flow behavior sensitive to strain rate and temperature, using artificial neural networks (ANNs). Plasticity is characterized by uniaxial tension and in-plane biaxial tension tests at temperatures of 0 °C and 20 °C with strain rates of 0.001 /s and 0.01 /s, and the results are used to calibrate the non-quadratic anisotropic Yld2000–3d yield function with respect to the plastic work. In order to predict the intricate plastic deformation with the temperature and strain rate effects, two distinct ANN models are developed; one to capture the strain hardening behavior and the other to predict the anisotropic parameters in the chosen yield function. The developed ANN models predict an unseen dataset well, which is intermediate testing conditions at a temperature of 10 °C and strain rate of 0.005 /s. The ANN models, being computationally stable and adhering to conventional constitutive equations, are implemented into a user material subroutine for the ductile fracture characterization of CP-Ti sheet using the hybrid experimental-numerical analysis. The favorable agreement between experimental data and numerical predictions, particularly using the ANN models with evolving anisotropic material parameters for the Yld2000–3d yield function, underscores the significance of the differential hardening effect on the ductile fracture behavior and highlights the capabilities of ANN models to capture the complex plastic behavior of CP-Ti. The key parameters including stress triaxiality, Lode angle parameter, and equivalent plastic strain at the fracture location are extracted from the simulations, enabling the calibration of ductile fracture models, namely Johnson-Cook, Hosford-Coulomb, and Lou-2014, and construction of fracture envelopes.