Isothermal compression tests were conducted on Mn-Cr-Ni-Mo steel at temperatures ranging from 1173 K to 1473 K and strain rates from 0.01 s–1 to 10 s–1 using a Gleeble-3800 thermal simulation tester. Four constitutive models for Mn-Cr-Ni-Mo steel, namely the Arrhenius model, Fields-Backofen model (F-B), original Johnson-Cook model (J-C), and the improved Johnson-Cook model (mJ-C) were established. A correlation coefficient (R) and the average absolute relative error (AARE) were employed to evaluate the predictive capability of these four models. Among them, the Arrhenius model exhibited superior accuracy in predicting the behavior of Mn-Cr-Ni-Mo steel. It and the isothermal thermal compression finite-element model were imported into Deform-3D software for a numerical simulation, aiming to analyze the distribution law of the equivalent stress field. A comparison was made between the time-stress data obtained from numerical simulation under different conditions and that from the isothermal compression tests. The results demonstrate good agreement between the time-stress curves of the numerical simulation and the experimental measurements, indicating that the established Arrhenius model can effectively simulate the thermal deformation of Mn-Cr-Ni-Mo steel. These research findings provide valuable fundamental data for simulating the plastic-deformation process of Mn-Cr-Ni-Mo steel.