© 2019 Multiple-principal element alloys known as high-entropy alloys have rapidly been gaining attention for the vast variety of compositions and potential combinations of properties that remain to be explored. Of these alloys, one of the earliest, the ‘Cantor alloy’ CrMnFeCoNi, displays excellent damage-tolerance with tensile strengths of ∼1 GPa and fracture toughness values in excess of 200 MPa√m; moreover, these mechanical properties tend to further improve at cryogenic temperatures. However, few studies have explored its corresponding fatigue properties. Here we expand on our previous study to examine the mechanics and mechanisms of fatigue-crack propagation in the CrMnFeCoNi alloy (∼7 μm grain size), with emphasis on long-life, near-threshold fatigue behavior, specifically as a function of load ratio at temperatures between ambient and liquid-nitrogen temperatures (293 K–77 K). We find that ΔKth fatigue thresholds are decreased with increasing positive load ratios, R between 0.1 and 0.7, but are increased at decreasing temperature. These effects can be attributed to the role of roughness-induced crack closure, which was estimated using compliance measurements. Evidence of deformation twinning at the crack tip during fatigue-crack advance was not apparent at ambient temperatures but seen at higher stress intensities (ΔK ∼ 20 MPa√m) at 77 K by post mortem microstructural analysis for tests at R = 0.1 and particularly at 0.7. Overall, the fatigue behavior of this alloy was found to be superior, or at least comparable, to conventional cryogenic and TWIP steels such as 304 L or 316 L steels and Fe-Mn steels; these results coupled with the remarkable strength and fracture toughness of the Cantor alloy at low temperatures indicate significant promise for the utility of this material for applications at cryogenic environments.