The response of the mixed layer depth (MLD) and subduction rate in the subtropical Northeast Pacific to global warming is investigated based on 9 CMIP5 models. Compared with the present climate in the 9 models, the response of the MLD in the subtropical Northeast Pacific to the increased radiation forcing is spatially nonuniform, with the maximum shoaling about 50 m in the ensemble mean result. The inter-model differences of MLD change are non-negligible, which depend on the various dominated mechanisms. On the north of the MLD front, MLD shallows largely and is influenced by Ekman pumping, heat flux, and upper-ocean cold advection changes. On the south of the MLD front, MLD changes a little in the warmer climate, which is mainly due to the upper-ocean warm advection change. As a result, the MLD front intensity weakens obviously from 0.24 m/km to 0.15 m/km (about 33.9%) in the ensemble mean, not only due to the maximum of MLD shoaling but also dependent on the MLD non-uniform spatial variability. The spatially non-uniform decrease of the subduction rate is primarily dominated by the lateral induction reduction (about 85% in ensemble mean) due to the significant weakening of the MLD front. This research indicates that the ocean advection change impacts the MLD spatially non-uniform change greatly, and then plays an important role in the response of the MLD front and the subduction process to global warming.