Refractory multi-principal element alloys (RMPEAs)have become a hotspot in materials science research in recent years due to their excellent high-temperature mechanical properties and broad application prospects. However, the unique deformation mechanisms and mechanical behaviors of the NbTaTiZr quaternary RMPEA under extreme conditions such as high temperature and high strain rate are still unclear, limiting its further design and engineering applications. In order to reveal in depth the dynamic response of this alloy on an atomic scale, this study develops a high-accuracy machine learning potential (MLP) for the NbTaTiZr quaternary alloy and combines it with large-scale molecular dynamics (MD) simulations to systematically investigate the effects of crystallographic orientation, strain rate, temperature, and chemical composition on the mechanical properties and microstructural evolution mechanisms of the alloy under compressive loading. The results show that the NbTaTiZr alloy exhibits significant mechanical and structural anisotropy during uniaxial compression. The alloy exhibits the highest yield strength when loaded along the [111] crystallographic direction, while it shows the lowest yield strength when compressed along the [110] direction, where twinning is more likely to occur. Under compression along the [100] direction, the primary deformation mechanisms include local disordering transitions and dislocation slip, with 1/2$ \left\langle{111}\right\rangle $ dislocations being the dominant type. When the strain rate increases to 10¹⁰ s^–1, the yield strength of the alloy is significantly enhanced, accompanied by a notable increase in the proportion of amorphous or disordered structures, indicating that high strain rate loading suppresses dislocation nucleation and motion while promoting disordering transitions. Simulations at varying temperatures indicate that the alloy maintains a high strength level even at temperatures as high as 2100 K. Compositional analysis further indicates that increasing the atomic percentage of Nb or Ta effectively enhances the yield strength of the alloy, whereas an increase in Ti or Zr content adversely affects the strength. By combining MLP with MD methods, this study elucidates the anisotropic characteristics of the mechanical behavior and the strain rate dependence of disordering transitions in the NbTaTiZr RMPEA under combination of high strain rate and high temperature, providing an important theoretical basis and simulation foundation for optimizing and designing novel material under extreme environments.