Predicting when and where materials fail is a holy grail for structural materials engineering. Development of a predictive capability in this domain will optimize the employment of existing materials, as well as rapidly enhance the uptake of new materials, especially in high-risk, high-value applications, such as aeroengines. In this article, we review and outline recent efforts within our research groups that focus on utilizing full-field measurement and calculation of micromechanical deformation in Ni-based superalloys. In paticular, we employ high spatial resolution digital image correlation (HR-DIC) to measure surface strains and a high-angular resolution electron backscatter diffraction technique (HR-EBSD) to measure elastic distortion, and we combine these with crystal plasticity finite element (CPFE) modeling. We target our studies within a system of samples that includes single, oligo, and polycrystals where the boundary conditions, microstructure, and loading configuration are precisely controlled. Coupling of experiment and simulation in this manner enables enhanced understanding of crystal plasticity, as demonstrated with case studies in deformation compatibility; spatial distributions of slip evolution; deformation patterning around microstructural defects; and ultimately development of predictive capability that probes the location of microstructurally sensitive fatigue cracks. We believe that these studies present a careful calibration and validation of our experimental and simulation-based approaches and pave the way toward new understanding of crack formation in engineering alloys.