The workpiece mass varies greatly due to large material removal rate when machining aeronautical thin-walled structure. The driving force of transmission system also changes greatly, which can affect the transmission system dynamics. In order to obtain the time-varying dynamics of machine tool transmission system, a dynamics model of the transmission system was established using the lumped parameter method considering load variation and friction characteristics of the slide block. The equivalent damping coefficient in feed direction was theoretically analyzed with the load variation. And the evolution of natural frequency and vibration response of transmission system is studied as well under different loads. The results show that a time-varying dynamics of transmission system is found when machining large material removal rate. The equivalent damping coefficient decreases as the load decreases, while the natural frequency and vibration amplitude increase as the load decreases. Finally, modal testing is performed to validate the theoretical analysis.