Fatigue remains a prevalent failure mode despite vast amounts of research. Demystifying the complexity of cyclic plasticity leading to fatigue crack initiation in ductile, polycrystalline metals could strongly leverage the experimental capability to probe "everywhere, all the time, at all resolutions''. While no single materials characterization technique can directly achieve this capability, pairing techniques with data-driven signature discovery may unlock indirect access. The fatigue is often attributed to rare material response events generating the "weakest link" in the material. In the expanse of thousands of grains within a polycrystal, it is a formidable challenge to discern which grains undergoing cyclic plasticity, will ultimately initiate cracks. In light of this challenge, this work pairs high energy X-ray diffraction microscopy (HEDM) techniques with signature discovery to devise methods for probing critical material response during in-situ cyclic loading. First, the "at all resolutions" aspect of the ideal capability is explored by combining far-field HEDM and high resolution electron backscatter diffraction (EBSD) measurements to identify an indirect signature of localized deformation. A signature-identified grain was tracked throughout the two cycles of loading to capture its mechanical behavior. Next, the "all the time" aspect is explored by applying real-time principal component analysis (PCA) to rapidly collected X-ray diffraction data. This analysis correlated the time-resolved X-ray data to grain-scale physical processes. Lastly, the preliminary aspects of "everywhere" are explored by incorporating far-field and near-field HEDM to elucidate the cyclic asymmetries of mechanical response throughout the polycrystal. These developments serve to advance the current understanding of cyclic plasticity leading to fatigue crack initiation.