The development of precious-metal microwires is associated with high research and production costs, primarily due to the elevated price of precious metal raw materials, the complexity of fine wire drawing processes, and the low manufacturing yield. This study establishes a cross-scale simulation framework for single-pass drawing of Au-27Pd-18Ag alloy microwires based on crystal plasticity finite element modeling (CPFEM). By integrating crystal plasticity theory with electron backscatter diffraction (EBSD) data obtained from annealed gold-based alloy wires, a two-dimensional polycrystalline model incorporating 255 realistic grain morphologies was constructed. A dislocation density evolution equation was introduced to characterize strain-hardening behavior, and model parameters were calibrated through a trial-and-error procedure, resulting in a deviation of less than 5% between the simulated and experimental tensile stress-strain curves. The results reveal the stress and strain distribution characteristics during the drawing process: surface grains exhibit pronounced stress gradients due to die compression and friction, while the strain distribution presents a non-uniform “low–high–low” pattern from the core to the surface. Furthermore, the findings confirm that grain orientation heterogeneity governs slip system activation through variations in the Schmid factor.