The Al80Mg5Li5Zn5Cu5 light-weight high-entropy alloy with globular microstructure was fabricated by isothermal heat treatment. The effects of isothermal temperatures and holding times on the semi-solid microstructure evolution were investigated. The results indicate that, with increase of the isothermal temperature, the average grain size increases and the spheroidization time shortens. With prolongation of holding time, the shape factor increases firstly and then decreases, and the average grain size decreases at first and then increases when the isothermal temperature is below 520 °C, however it increases gradually at 540 °C. The optimal semi-solid microstructure is obtained at 520 °C for 30 min, whose shape factor and average grain size are 0.90 and 56.4 μm, respectively. Compared with as-cast Al80Mg5Li5Zn5Cu5 light-weight high-entropy alloy, the compressive strength and plasticity of semi-solid Al80Mg5Li5Zn5Cu5 light-weight high-entropy alloy are increased by 36% and 108%, respectively. The formation of semi-solid microstructures includes three stages: melting separation, spheroidization, and coarsening growth. The sluggish diffusion effect of Al80Mg5Li5Zn5Cu5 light-weight high-entropy alloy leads to a low coarsening rate, resulting in slow grain growth.