Al20Cr5Fe50Mn20Ti5 medium-entropy alloy (MEA) coatings with different preparation process parameters were successfully fabricated by laser cladding (LC) on Inconel 718 Ni-alloy substrate. Comparison of two coatings with optimal macroscopic morphology, and the phase, micro-structure and hardness were characterized using SEM, XRD, and EBSD. The thermal stability performance of the two MEA coatings was systematically analyzed by combining phase diagram calculation and experimental tests. Compared to the substrate, the frictional wear properties of the MEA coatings at 400 °C, 600 °C and 800 °C were systematically analyzed. The results show that Al20Cr5Fe50Mn20Ti5 MEA coatings with two different parameters formed a good metallurgical bond with the substrate, contained BCC, FCC and Ti-rich phases, and both had a good thermal stability at the range of room temperature to 1000°C. The refinement of grain size and the enhancement of dislocation density improved Al20Cr5Fe50Mn20Ti5 MEA coatings wear properties. The generation of Ti-rich phase enhanced the wear performance, while excessive fusion of Ti elements into the coating caused oxidation at high temperatures to generate brittle phases, which reduced wear performance and led to coating failure. Through this study, new designed MEA system with low cost advantage can be applied in high temperature environment.