In this paper, ultrasonic guided wave propagation in metallic structures is investigated using multiscale modeling. Unlike the conventional approach of damage detection using macro scale finite element (FE) based wave propagation model and artificially induced damage in the structure, our approach obtains damage initiation information from a multiscale damage criterion. This criterion incorporates crystal plasticity at the microscale and results in a damage tensor, which is driven by modification of strain energy density on each potential slip system. The damage tensor is averaged using the Kreisselmeier-Steinhauser function approach to calculate the damage index for a meso representative volume element (RVE). The RVE is placed at the location of highest possible damage in a macroscale 3-D FE model to simulate plastic zone initiation under fatigue loading. The 3-D FE model in which the RVE was incorporated was able to simulate guided wave propagation at ultrasonic frequency ranges. An experiment was conducted to validate the proposed 3-D model, and the interaction between guided waves and incipient damage under various loading conditions is discussed.