β-21S titanium alloy sheet fatigue crack growth behavior was investigated at 25°C and 175°C under constant amplitude (R = 0.1 and 0.5) and miniTWIST flight spectra. Based upon nominal ΔK values, constant amplitude fatigue crack growth behavior at 175°C was either similar to (R = 0.1), or slightly better than (R = 0.5) 25°C. With crack closure taken into account, the fatigue crack growth curves at 175°C, plotted as a function of Keff, were shifted to the left of the fatigue crack growth curves at 25°C at near threshold values. Under flight spectra conditions, fatigue crack growth life at 175°C was 40 to 90 percent longer than at 25°C. Flight spectra life calculations using NASA/FLAGRO based upon constant amplitude fatigue crack growth data, were primarily conservative but in good agreement with experimental data. Fatigue crack growth was transgranular with crystalline facets and striations that were evident at higher constant amplitude fatigue crack growth rates and with the miniTWIST spectra. Striations were observed to a limited extent at threshold and near threshold conditions at 25°C, but not at 175°C. Based upon desirable constant and variable amplitude fatigue crack growth and fatigue/fracture crack morphology, this β-21S sheet alloy appears to be an acceptable material for damage tolerant aerospace situations between 25°C and 175°C.