We study the dynamics and unbinding transition of vortices in the compact anisotropic Kardar-Parisi-Zhang (KPZ) equation. The combination of non-equilibrium conditions and strong spatial anisotropy drastically affects the structure of vortices and amplifies their mutual binding forces, thus stabilizing the ordered phase. We find novel universal critical behavior in the vortex-unbinding crossover in finite-size systems. These results are relevant for a wide variety of physical systems, ranging from strongly coupled light-matter quantum systems to dissipative time crystals.