Studies on microstructurally small fatigue cracks have illustrated that heterogeneous microstructural features such as inclusions, pores, grain size distribution as well as precipitate size distribution and volume fraction create stochasticity in their behavior under cyclic loads. Therefore, to enhance safe-life and damage-tolerance approaches, accurate modeling of the influence of these heterogeneous microstructural features on microstructurally small crack formation and growth from stress raisers is necessary. In this work, computational micromechanics was used to predict the high cycle fatigue of microstructurally small crack formation and growth in notched polycrystalline nickel-base superalloys and to quantify the variability in the driving force for formation and growth of microstructurally small crack from notch root in the matrix with non-metallic inclusions. The framework involves computational modeling to obtain three-dimensional perspectives of microstructural features influencing fatigue crack growth in notched nickel-base superalloys, which accounts for the effects of nonlocal notch root plasticity, loading, microstructural variability, and extrinsic defects on local cyclic plasticity at the microstructure-scale level. This approach can be used to explore sensitivity of minimum fatigue lifetime to microstructures. The simulation results obtained from this framework were calibrated to existing experimental results for polycrystalline nickel-base superalloys.