The phase stability and equilibria of carbon dioxide are investigated from 125–325 K and 1–10 000 atm using extensive molecular dynamics (MD) simulations and the Two-Phase Thermodynamics (2PT) method. We devise a direct approach for calculating phase diagrams, in general, by considering the separate chemical potentials of the isolated phase at specific points on the P–T diagram. The unique ability of 2PT to accurately and efficiently approximate the entropy and Gibbs energy of liquids allows for assignment of phase boundaries from relatively short (∼100 ps) MD simulations. We validate our approach by calculating the critical properties of the flexible elementary physical model 2, showing good agreement with previous results. We show, however, that the incorrect description of the short-range Pauli force and the lack of molecular charge polarization lead to deviations from experiments at high pressures. We, thus, develop a many-body, fluctuating charge model for CO2, termed CO2–Fq, from high level quantum mechanics (QM) calculations that accurately capture the condensed phase vibrational properties of the solid (including the Fermi resonance at 1378 cm−1) as well as the diffusional properties of the liquid, leading to overall excellent agreement with experiments over the entire phase diagram. This work provides an efficient computational approach for determining phase diagrams of arbitrary systems and underscores the critical role of QM charge reorganization physics in molecular phase stability.