Fatigue of structural materials is a leading cause of failure and has motivated fatigue-resistant design to eliminate risks to human lives. Majority of conventional materials, including advanced steels and Ni-based superalloys, exhibit limited fatigue endurance limits at ambient temperature. With this in mind, we designed a Cu-containing FeMnCoCrSi high entropy alloy which exhibits a normalized fatigue ratio of ∼0.62 UTS (ultimate tensile strength). Our design approach was based on (a) engineering the γ phase stability to attain sustained work hardening (WH) through delayed γ (f.c.c.) → ɛ (h.c.p.) transformation to hinder fatigue crack propagation and (b) an ultrafine grained (UFG) microstructure to delay crack initiation. We verified that a UFG γ dominant microstructure could provide opportunities for enhanced fatigue resistance, as sustained WH activity strengthened the material locally in the crack plastic zone, thereby validating our expectation that the combination of UFG and transformation induced plasticity (TRIP) is a path to design the next generation of fatigue-resistant alloys. © 2019 Elsevier Ltd