The study of the impact of climate change on permafrost and the response mechanism in the Upper Irtysh River Basin can help to comprehensively understand the impact of climate change and grasp the development of coping strategies. In this paper, the one-dimensional heat conduction equation is used as the core to propose a model for calculating the distribution of permafrost in the upper Irtysh River Basin and the boundary conditions for solving the model, and the model is simulated and solved by using the general form of partial differential equations in the COMSOL Multiphysics finite element analysis software. Subsequently, the simulation results and regression equations are combined to investigate the driving effect of meteorological data changes on permafrost depth distribution changes. The simulation results found that the meteorological factor regression model could explain 30.6% of the variation in maximum permafrost depth, with mean annual relative humidity driving permafrost depth to the greatest extent (Beta = -0.251). This paper finds that the driving effect of meteorological factors on permafrost depth change provides a new perspective for understanding the dynamical mechanism of permafrost change in the upper Irtysh River Basin, and also provides a scientific basis for predicting and responding to the impact of future climate change on permafrost.