Seismic reliability analysis of actual slopes considering the spatial variability of soil materials is crucial. However, for the discretization of large-scale random fields, high-precision finite element analysis and analysis of small failure probability events, the random analysis of slopes under seismic loads is inefficient. To address this situation, this study proposes a collaborative reliability analysis framework based on the modified linear estimation method (MLEM) and optimized subset simulation (OSS). First, the random field of the uncertain parameters of the Jinping-I left bank slope model is efficiently discretized by the MLEM, and a sensitivity analysis is carried out. Then, considering the adoption of different degrees of cross-correlation of the sensitive random parameters, the OSS method is used to perform random finite element analysis on the coarse mesh model. Finally, the fine mesh samples are obtained according to the response conditioning method (RCM). The MLEM is used to ensure the consistency of the two sets of random fields, and the seismic failure probability and reliability index of the slope under different cross-correlation coefficients of uncertain parameters are obtained. The results suggest that the degree of cross-correlation of parameters has a great influence on the seismic reliability of the slope. Considering that the shear strength parameters of geotechnical materials are often negatively correlated, the fine analysis based on a fine model is necessary.