Due to the complex operation conditions in a power transformer, an oil-impregnated pressboard (OIP) simultaneously suffers from thermal, electrical, and mechanical stress. Since most research studies have paid much attention to thermal or electrical aging of OIPs, this paper analyzes the effects of long-term mechanical vibrations on cellulose degradation in OIPs under simultaneous multi-stress. The aging experiments were firstly conducted at 130 °C, with a DC electric voltage of +6 kV, vibration amplitude of 10–50 μm, and vibration frequency of 100–300 Hz. The finite element analysis (FEA) of the pressboard vibration model was then performed on Abaqus to investigate the time–frequency domain characteristic parameters of compressive stress on the pressboard under varied vibration frequencies and amplitudes. The FEA results reveal that compressive stress on the pressboard in a multi-stress aging experiment coincided with the axial compressive stress on the insulation spacers in an SZ-50000/110 transformer. Moreover, combined with the degree of polymerization (DP) of cellulose, the effects of long-term vibration on cellulose degradation are reflected in two ways: the increase in compressive stress on the pressboard generates more links available for degradation, while more high frequency harmonic components in compressive stress accelerate the reaction rate in cellulose degradation.