In traditional seismic studies of transmission lines, the tower base is typically modeled with fixed constraints, and the effects of soil-structure interaction (SSI) and varying ground motions along soil depth are rarely considered. This simplification leads to inaccurate seismic performance assessment. To address this problem, this work established three finite element models of a transmission tower-line system (ignoring SSI, considering SSI but ignoring varying ground motions along soil depth, and comprehensively considering SSI and varying ground motions). Incremental dynamic analysis was employed to develop probabilistic seismic demand models for different performance states. Fragility analysis was also performed to clarify the impacts of SSI and varying ground motions on the seismic response of the transmission tower-line system. Results demonstrate the following: (1) SSI notably amplifies the seismic response of the tower-line system. (2) Ignoring the spatial variation effect of ground motions along soil depth leads to an overestimation of structural seismic performance. (3) Under varying ground motions along soil depth, the pile length at the tower base is inversely proportional to the seismic performance. This study underscores the necessity of incorporating SSI and vertically varying ground motions in the seismic design and analysis of transmission tower-line systems.