© 2018 American Society of Civil Engineers. Half-through steel plate girder bridges are widely used across the United Kingdom's railway network. However, few studies have investigated their real in-service behavior. Concurrently, the use of advanced sensor systems, such as those utilizing fiber-optic sensors, have begun to find widespread use in structural health monitoring due to their high accuracy and long-term stability and durability. In this paper, the real performance of a newly constructed skewed half-through plate girder railway bridge was assessed using an integrated fiber optic monitoring system installed during the bridge's construction. Monitoring data recorded during the passage of 12 separate trains consisted of strains measured along the length of the main steel plate girders and crossbeams. Based on available design and construction information, a three-dimensional finite-element model capable of simulating the railway bridge's response was constructed and used to investigate and provide comparisons with monitoring results of the performance of such bridges under passing trains. The influence of track cant on load distribution between the two main girders was discussed, and the live load utilization percentage of the main girders was estimated to be approximately 37% of its design capacity. In addition, the effect of different transverse crossbeam end-connection details (pinned or moment connected) and the influence of axle load distribution through track ballast on the overall response of the bridge structure were evaluated. The results obtained in this study have not only led to the establishment of a comprehensive performance baseline for the newly constructed bridge for long-term condition monitoring but may also be used for improving the design and in-service structural evaluation of such bridges.