High-entropy functional materials are of great interest in materials science and engineering community. In this work, ab initio electronic structure calculations of the phase stability and magnetic transition temperature of AlxCr0.25MnFeCo0.25−yNiy (x = 0–0.5, y = 0–0.25) alloys were performed to screen for compositions showing promising magnetocaloric properties in the vicinity of room temperature. The selected Al0.44Cr0.25MnFeCo0.05Ni0.2 alloy was synthesized via a rapid solidification technique and systematically characterized with respect to its structural and magnetocaloric properties. The results indicate that this alloy possesses a homogeneous microstructure based on an underlying body-centered cubic lattice and has a Curie temperature of ∼340 K. The temperature dependence of the adiabatic temperature change was evaluated using both direct and indirect methods. The ab initio-assisted design of 3d-metal-based high-entropy alloys, explored here, is intended to contribute to the development of magnetic refrigerators for room-temperature applications.