Abstract Developing ultrathin giant magnetostrictive materials above room temperature creates a versatile platform for straintronic and spintronic applications because they can provide significant spin–lattice interaction on the nanoscale. Nevertheless, due to the suppression of magnetic ordering by thermal fluctuations, there are fewer ultrathin room‐temperature magnetic materials available, not to mention ultrathin giant magnetostrictive materials at room temperature. Here, the ultrathin single‐crystal Fe x Mn 1–x Ga 4 is reported with above‐room‐temperature Curie temperature ( T C , ≈ 324 K) and giant magnetostriction (magnetostrictive coefficient λ, –1670 ppm). The giant magnetostriction originates from the large magnetic anisotropy energy of Fe x Mn 1–x Ga 4 , which is caused by the strong spin coupling between d xy and d yz of Fe atoms due to the same spin channel near the Fermi level. The Villari effect is also observed in the Fe x Mn 1–x Ga 4 , in which the coercivity field increases dramatically by more than 300% at a tiny‐scale applied strain of 0.69%. This work provides an avenue to realize giant magnetostriction in ultrathin materials at room temperature, laying the foundation for low‐power‐consumption, integrative, and high‐performance nanoelectromechanical applications.