Regional comprehensive transportation infrastructures constitute the fundamental basis for the development of inland urban agglomerations. To elucidate the role of comprehensive transportation in shaping the spatial organization and expansion of urban agglomerations, this study takes the Yangtze River Middle Reaches Urban Agglomeration (YRMRUA) as a case example. It examines the spatial relationships between transportation network layout and spatial expansion patterns using fractal dimension based on traffic accessibility, traffic-weighted linear density, and Pearson correlation analysis. The key findings of this study are as follows: (1) The YRMRUA exhibits a partial fractal growth pattern influenced by transportation development, which indicates that the comprehensive transportation has a significant but limited impact on YRMRUA. (2) There is a moderate correlation between traffic-weighted linear density and spatial expansion intensity within YRMRUA. (3) Specific groups such as the Wuhan–Ezhou–Huanggang–Huangshi group, Changsha–Zhuzhou–Xiangtan group, and Nanchang–Yichun group have formed in areas where transportation development and spatial expansion are at the forefront. (4) Different modes of transportation, including waterway transportation, railway transportation, and road transportation, have varying effects on spatial expansion. The integration of these modes forms the fundamental framework of urban agglomerations.