Femtosecond laser machining, characterized by a small heat-affected zone, high precision, and non-contact operation, is ideal for processing metallic glasses. In this study, we employed a simulation method that combines the two-temperature model with molecular dynamics to investigate the effects of fluence and pulse duration on the femtosecond laser ablation of Cu50Zr50 metallic glass. Our results showed that the ablation threshold of the target material was 84 mJ/cm2 at a pulse duration of 100 fs. As the pulse durations increased, the maximum electron temperature at the same position on the target surface decreased, while the electron−lattice temperature coupling time showed no significant difference. As the absorbed fluence increased, the maximum electron temperature at the same position on the target surface increased, while the electron−lattice temperature coupling time became shorter. The surface ablation of the target material was mainly induced by phenomena such as melting, spallation, and phase explosion caused by femtosecond laser irradiation. Overall, our findings provide valuable insights for optimizing the femtosecond laser ablation process for metallic glasses.