This study leveraged the high-throughput experiments and high-throughput calculations to study the thermodynamic and kinetic behaviors, and mechanical properties of different alloy systems. CALculation of PHAse Diagrams (CALPHAD) and machine learning (ML) are two computational approaches to predict the phase equilibria of alloys and were adopted to study the phase formation of 2436 high-entropy alloys (HEAs). HEAs were found to form 100% BCC at VEC < 6.87 and form essentially 100% FCC at VEC > 9.16 experimentally, this is consistent with the CALPHAD calculations (VEC = valence electron concentration). ML trained models can reach more than 90% accuracy in predicting BCC/B2, BCC/B2 + FCC, and FCC phases. An autonomous materials search engine (AMASE) method was developed by collaborators to map the phase diagram of the thin-film Sn-Bi system in a closed-loop method, which speeds up the phase diagram mapping and thermodynamic assessment processes over the traditional grid mapping. In the NSF sponsored project, the diffusion-multiple approach was employed to map the phase diagrams of the ternary subsystems of the Cr-Fe-Ni-Nb system. Wavelength-dispersive spectroscopy (WDS) mapping was adopted to measure the compositions in the triple-junction areas of diffusion multiples, leading to improve the efficiency of constructing phase diagrams in comparison with the previous practice of using electron probe microanalysis (EPMA) line scans. The WDS mapping method was demonstrated in the experimentally determined ternary phase diagram of Fe-Nb-Ni at 1100 °C. The measured tie-line data was then provided to collaborators to obtain more accurate predictions of the phase stability of topologically close-packed (TCP) phases for future improvement of the Ni-based thermodynamic databases. Besides thermodynamic calculations, mobility assessments of 25 binary systems with single-phase BCC or FCC structure were performed using the 1-parameter Z-Z-Z binary diffusion model. The data will be useful input to robust diffusion coefficient (mobility) databases. Hardness testing was performed to study the solid solution hardening effects on eight Mg-X (X = Al, Ca, Ce, Gd, Li, Sn, Y, Zn) binary systems using liquid-solid diffusion couples and on three binary systems (Mo-Nb, Mo-Ta, and Nb-Ta) of refractory elements using novel macro-gradient samples made by electron beam welding of stacked wedge-samples.