Span lengths of newly constructed cable-stayed railway bridges continue to show increases relative to those of older bridges. Accompanying such increases is the importance of ensuring that vibrations of long-span cable-stayed bridges satisfy both safety and serviceability requirements, particularly for bridges that support train passages. In contrast to modern design of bridges that support roadway vehicles, current methods for analyzing cable-stayed railway bridges do not yet typically account for coupling effects that may occur between cables and the surrounding bridge structure during train passages. This paper presents a computational framework for the nonlinear dynamic analysis of railway bridges based on a coupled train–bridge analytical model and investigates the significance of accounting for cable-related coupling effects. A case study is then carried out, where coupled dynamic responses of cables, towers, and girders of an in-service railway bridge are computed and compared to those obtained using an uncoupled approach. These comparisons demonstrate the merits of accounting for coupling phenomena when computing dynamic characteristics of cable-stayed railway bridges and highlight benefits of the coupled analysis approach in bridge design applications.