The ingot of S31254 super austenitic stainless steel (SASS) was annealed at 1220 °C for 70 h to eliminate the segregation of Mo element, and the grain size grows to the level of millimeter. The stress–strain response and microstructural evolution of coarse-grained S31254 SASS were investigated by hot compression tests in the temperature range of 950–1250 °C and strain rate range of 0.001–10 s−1. The results showed that the energy required for plastic deformation improved with the increase of strain rate and the decrease of deformation temperature. The hot deformation activation energy was calculated to be 542.91 kJ·mol−1 through the regression analysis of hyperbolic-sine function, and the constitutive equation was established. Processing maps were constructed, and two optimal hot working parameters ranges were clarified. Due to the low fraction of grain boundaries, the main deformation mechanism of coarse-grained S31254 SASS was dynamic recovery. However, when the deformation temperature improved to 1250 °C, recrystallized grains began to nucleate and grow along with the band-like structure within the austenitic grains. When the deformation temperature is 950–1150 °C, the microstructural stability of S31254 SASS under tension stress was excellent. However, when the temperature and the strain rate were 1250 °C and 0.5 s−1 respectively, the microstructural stability deteriorated resulting from the formation of δ-ferrite phase and local melting of austenitic grain boundaries.