AbstractUsing high-throughput first-principles calculations to search for layered van der Waals materials with the largest piezoelectric stress coefficients, we discover NbOI₂ to be the one among 2940 monolayers screened. The piezoelectric performance of NbOI₂ is independent of thickness, and its electromechanical coupling factor of near unity is a hallmark of optimal interconversion between electrical and mechanical energy. Laser scanning vibrometer studies on bulk and few-layer NbOI₂ crystals verify their huge piezoelectric responses, which exceed internal references such as In₂Se₃ and CuInP₂S₆. Furthermore, we provide insights into the atomic origins of anti-correlated piezoelectric and ferroelectric responses in NbOX₂ (X = Cl, Br, I), based on bond covalency and structural distortions in these materials. Our discovery that NbOI₂ has the largest piezoelectric stress coefficients among 2D materials calls for the development of NbOI₂-based flexible nanoscale piezoelectric devices.