Thermomechanical processing routes are used to produce microstructures that minimize plastic strain localization at the sub-grain scale in a polycrystalline γ − γ' nickel- based superalloy. This novel approach is made possible by the use of innovative experimental tools and statistical data analysis that capture slip events over large represen- tative fields of view. Results are correlated to conventional observations of fatigue crack initiation and early stage of propagation. The effect of coherent twin boundaries and primary γ' precipitates on fatigue properties and plastic localization is detailed.