Facile nucleation and growth of bilayer Ag(110) islands on NiAl(110) is observed by STM for Ag deposition at temperatures as low as 127 K. Density functional theory analysis for supported Ag films determines adatom adsorption energies (which favor bilayer islands), interaction energies, and diffusion barriers. Analysis of an atomistic lattice-gas model incorporating these energies elucidates the role of strongly anisotropic interactions in enabling the upward mass transport needed for bilayer island formation.