The aging and failure of transformer bushing seals under multi-factor effects are significant causes of oil leakage incidents. However, their failure mechanisms under combined environmental stressors remain inadequately understood. This study presents a comprehensive investigation into the aging behavior and failure mechanisms of nitrile rubber (NBR) and fluoroelastomer (FKM) sealing materials subjected to single and multi-factor aging conditions, including thermo-oxidative, hygrothermal, hygrothermal–compression, and hygrothermal–compression–salt environments. NBR undergoes severe degradation under multi-factors, dominated by additive loss and molecular chain crosslinking. At high temperatures, large-scale molecular chain scission occurs, along with increased compression set, microscopic morphological damage, and filler precipitation. In contrast, FKM exhibits excellent stability thanks to its C-F main chain. Stress synergy significantly accelerates the failure of both materials. These findings highlight the need for multivariate analysis to support reliable condition assessment and lifetime prediction and to inform sealing material selection and proactive grid maintenance.