High-entropy alloys have gained widespread concern in response to the increased requirements for future high-temperature structural superalloys. By combining phase-diagram calculations with microhardness, compression behavior measurements at room temperature, and elevated temperature conditions, the very important role of the Cr element on the microstructure and properties is deeply revealed, which provides candidates materials for future high-temperature alloy applications. The increment of Cr favors the regulation of the two-phase fraction and distribution. The thermodynamic calculations illustrate that the density and melting point of the HEAs showed an increasing trend with the increase of the Cr content. The typical worm-like microstructure of the Cr0.6alloy with a dual BCC structure was detected. Meanwhile, on the one hand, the increment of the Cr elements results in a considerable optimization of the mechanical properties of the alloy in terms of strength and ductility at room temperature. The corresponding compressive strength and plasticity of Cr0.6alloy at room temperature are 3524 MPa and 43.3%. On the other hand, the high-temperature mechanical properties of the alloy are greatly enhanced. At 1000 °C, the yield strength of the Cr0.6alloy is about 25 MPa higher than that of the Cr0.4alloy. The superior mechanical properties are attributed to the pronounced work-hardening response, and the work-hardening behavior of Cr-containing HEAs was systematically analyzed by employing the modified Ludwik model. The higher content of Cr helps the resistance of the local deformation response, improving the nonuniform strain and promoting the balance of strength and ductility of the alloys.