Microstructure-sensitive simulation-based strategies for modeling fatigue life reduction in cyclically loaded notched components offer a means to augment costly experiments and to project performance of microstructures not yet processed. To advance design tools for notch fatigue resistance in aircraft gas turbine engine components, we present a formulation that links microstructure heterogeneity (grain size distribution) to size effects and fatigue scatter in notched polycrystalline Ni-base superalloy IN100 specimens. Simulated double-edged notched specimens with various notch radii are subjected to completely-reversed, quasistatic, isothermal (650 °C), strain-controlled loading at three different strain amplitudes. Polycrystal plasticity and experimentally-calibrated crack formation/growth laws are used to correlate cyclic plastic slip to the probability of forming and propagating a crack from grain scale to a transition crack length at which LEFM is applicable. Probabilistic strain-life and cumulative distribution function (CDF) plots show that larger notch sizes display a larger notch size effect and fatigue knock-down effect. The proposed CDF can be determined for any failure probability and number of cycles, which has implications for minimum fatigue life design of aircraft gas turbine engine components.