Based on a practical engineering case of seismic strengthening, this paper used the enlarging cross-section method and an external self-centering substructure to improve the seismic performance and seismic resilience of existing frame structures. Among them, the external self-centering substructure included setting a self-centering precast beam and diagonal braces. Utilizing the OpenSees finite element platform, a seismic fragility analysis was carried out to compare the improvements in seismic performance and seismic resilience before and after strengthening. The analysis results show that the proposed modelling method could be simulated satisfactorily. The maximum inter-story drift and the residual inter-story drift of the strengthened frame structures decreased significantly under the same peak ground acceleration. The peak ground acceleration of the strengthened frame structures significantly increased under different performance levels. Additionally, the exceedance probability of the strengthened frame structures was obviously reduced, which reflected that the seismic performance and seismic resilience of the strengthened frame structures were significantly improved.