Local cyclic plasticity near stress concentrations governs the fatigue crack initiation in cyclicly loaded Ni-based single-crystal superalloys, but has not been well studied and understood. The first of its kind transmission electron microscopy (TEM)-based site-specific study of plasticity in the crack initiation region in a notched single-crystal superalloy subjected to fatigue testing at 800 °C, coupling it with microstructure-based crystal plasticity modeling, is presented. Detailed TEM examinations show that local plasticity near the notch significantly differs from bulk plasticity, featuring high dislocation densities and distinctive arrangements of dislocation pairs within γ’ precipitates. It further shows that the increased local stresses alone are responsible for the increase in dislocation density and extensive γ’ shearing, but not solely for the distinctive arrangement of dislocation pairs seen in the notch vicinity, thus highlighting the considerable role played by the local variations in loading rates and stress state surrounding the notch. The results of this work provide new fundamental insights into the deformation micromechanisms leading to fatigue crack initiation in single-crystal superalloys.