MXenes have been studied as promising 2D materials for various applications such as semiconductors, energy storage, supercapacitors, electromagnetic shielding, sensors, batteries, and adsorbents. In particular, 2D high-entropy MXenes are expected to improve the physical or chemical properties of MXenes through the combination of various transition metal compositions. However, it is challenging to experimentally investigate novel high-entropy MXene compositions owing to time and cost limitations. In the present study, using first-principles calculations, the synthesizability of high-entropy MXenes was determined by evaluating the thermodynamic stability and exfoliation possibility of high-entropy MAX phases, which are precursors of high-entropy MXenes. The high-entropy MXenes can be easily synthesized from few-layered and Al-based HE-MAX phases, which are composed of Ti, Nb, and Ta. Additionally, the thermodynamic stability and exfoliation possibility of high-entropy MAX phases are highly correlated with the lattice distortion factors (the standard deviation of bond length and differences in atomic radii) and the differences in the bond lengths of M-A and M-X, respectively. Out of 756 high-entropy MAX phase candidates, 146 high-entropy MXene compositions were estimated to be synthesizable. Furthermore, we successfully synthesized two novel high-entropy MXenes, (TiVNbTa)(2)C and (TiVNbHfTa)(2)C, which are expected to be highly synthesizable through our first-principles calculations.