Most high-entropy alloys and medium-entropy alloys (MEAs) possess outstanding mechanical properties. In this study, a series of lightweight nonequiatomic Al50–Ti–Cr–Mn–V MEAs with a dual phase were produced through arc melting and drop casting. These cast alloys were composed of body-centered cubic and face-centered cubic phases. The density of all investigated MEAs was less than 5 g/cm3 in order to meet energy and transportation industry requirements. The effect of each element on the microstructure evolution and mechanical properties of these MEAs was investigated. All the MEAs demonstrated outstanding compressive strength, with no fractures observed after a compressive strain of 20%. Following the fine-tuning of the alloy composition, the Al50Ti20Cr10Mn15V5 MEA exhibited the most compressive strength (~1800 MPa) and ductility (~34%). A significant improvement in the mechanical compressive properties was achieved (strength of ~2000 MPa, strain of ~40%) after annealing (at 1000 °C for 0.5 h) and oil-quenching. With its extremely high specific compressive strength (452 MPa·g/cm3) and ductility, the lightweight Al50Ti20Cr10Mn15V5 MEA demonstrates good potential for energy or transportation applications in the future.