The thermal regime of soil is vital for determining the presence and thermal stability of permafrost. To study long-term changes in the permafrost thermal regime in the Headwater Area of the Yellow River (HAYR), a mathematical model for soil heat transfer to simulate the dynamics of ground temperatures at six boreholes using the HYDRUS-1D model. The model’s reliability and applicability were confirmed through parameter calibration. Changes in the permafrost thermal regime from 1979 to 2018 in the HAYR were then simulated using monthly air temperature data from the China Meteorological Forcing Dataset (CMFD). Model simulations revealed an abrupt change in the mean annual ground temperature in the HAYR after 1999. Prior to 1999, the changing rates were from -0.037 to 0.026 °C/a, whereas after 1999, they ranged from 0.0059 to 0.12 °C/a. The abrupt increase in mean annual air temperature in 1998 and the occurrence of extreme climate disasters in 1999 were identified as the primary reasons for the sudden changes in the permafrost thermal regime in 1999. The rise in permafrost temperature and decrease in its thermal stability are expected to impact water resource conservation and biogeochemical cycles. This study provides scientific and technological support for understanding the response patterns of plateau permafrost to climate change and strengthening the zoning and control of the ecological environment in the HAYR.