Understanding fatigue crack initiation in ductile metals remains a significant challenge for engineers despite decades of research. In this work, high energy x-ray diffraction techniques and analysis methods are implemented to nondestructively monitor structural changes within grains of polycrystals during fatigue loading conditions. First, experimental results are presented from a fully reversed incremental step test performed on a precipitation strengthened copper alloy. Crystal plasticity modeling results are compared to the experiments to identify similarities and differences in structural heterogeneity across four target grains. Next, a pure copper sample is examined, and x-ray diffraction-based metrics are developed to characterize the heterogeneity of orientation and strain across each grain. Hundreds of grains within the pure copper and copper alloy samples are compared though these metrics to reveal significant differences in the character of their grain-scale deformation during cycling. Finally, a pure copper sample is tested to a relatively large number of cycles. The experimentally measured heterogeneity metric values for each grain are superimposed onto a three-dimensional grain map to provide insight into the spatial distribution of deformation across the aggregate.