A high-throughput scheme coupling two-dimensional (2D) diffusion simulations and diffusion triple experiments was used to evaluate the atomic mobilities in face-centered cubic Ni–Cu–Fe alloys. Before the atomic mobility evaluation, the thermodynamic parameters for the fcc and L12 phases were slightly modified to reproduce the phase equilibria between the two phases. The measured one-dimensional diffusion profiles in areas far from the triple conjunction in the diffusion triples were well reproduced using the atomic mobilities for the binary subsystems. The ternary interaction parameters were directly adjusted based on the 2D composition distributions in the central area of the diffusion triples annealed at varying temperatures. The reliability of the composition- and temperature-dependent mobilities was confirmed by comparing the calculated results with both the measured 2D composition profiles obtained in this study and the experimental diffusion data in the literature, including tracer and interdiffusion coefficients, composition profiles, and diffusion paths of diffusion couples. The good agreement of the comparison results demonstrated the reliability of the high-throughput scheme based on 2D diffusion. Moreover, only two diffusion triples were required in the case of Ni–Cu–Fe, which dramatically improved efficiency in comparison to the diffusion couple method. This high-throughput scheme is expected to significantly accelerate the development of atomic mobility databases for multicomponent alloys.