A meso-scale modeling approach is used to relate the local microstructural strength and fracture resistance to the macro-scale failure response of spot welds in hot-stamped ultra-high strength automotive steels. Two alloys, Usibor® 1500-AS and Ductibor® 1000-AS are considered, with a range of weld schedules and loading orientations, to promote a number of different failure modes. Detailed characterization of the microstructure and hardness variation occurring within the welded connections was performed. Tensile and V-bend tests were performed on tempered martensite samples with hardness levels similar to those observed in the HAZ in order to characterize the heat-affected zone (HAZ) properties. Local constitutive flow behaviour and fracture loci were developed for a range of material hardness values and were implemented in detailed 3D finite element models to predict damage progression, failure modes (pull-out versus interfacial), and load-displacement response of the spot welds under shear and normal loading. The results showed that the presence of a transient softened zone at the fusion boundary alters the failure mode and its location, which was accurately predicted by the meso-scale models. The models were able to predict the load-displacement responses with maximum relative error of 6.3 % for the measured peak load.