The V–Zn system was investigated by a combination of CALPHAD modeling with key experiments and first-principles calculations. Based on a critical literature review, one diffusion couple and nine alloys were designed to reinvestigate the stabilities of the phases reported in the literature. The samples were annealed and cooled under different conditions, followed by examination with X-ray diffraction and scanning electron microscopy with energy-dispersive X-ray spectrometry. Four phases ((V), (Zn), V Zn 3 and V 4Zn 5) were confirmed to exist in the phase diagram, while V Zn 16 and V 3Zn were not observed. By means of first-principles calculations, the enthalpies of formation for V Zn 3 and V 4Zn 5 were computed to be −4.55 kJ mol-atoms −1 and −4.58 kJ mol-atoms −1, respectively. A set of self-consistent thermodynamic parameters for this system was obtained by considering the reliable experimental phase diagram data and the enthalpies of formation acquired from first-principles calculations. The calculated V–Zn phase diagram agrees well with the experimental data.