Highway bridges are critical in facilitating transportation and ensuring emergency response effectiveness, particularly in earthquake-prone regions. While extensive research has been conducted on the seismic behavior of concrete bridges, uncertainties persist regarding the impact of in-span hinges on irregular bridge configurations commonly encountered in real-world scenarios. This research examines the seismic behavior of reinforced concrete slab bridges with different span irregularities. The seismic response of bridges with different span configurations is systematically analyzed through numerical simulations and analytical investigations. Key parameters, including the length ratio between left and right spans, are varied to assess their influence on bridge performance during seismic events. The study quantifies structural responses such as displacements, stresses, reactions, and moments, providing valuable insights into the structural behavior and vulnerabilities of irregular bridge configurations. The results highlight the significance of considering span irregularities in bridge design and retrofitting practices to enhance seismic resilience. Moreover, optimal length ratios between spans are identified to mitigate potential damage and improve overall structural performance. These findings aid in creating efficient design principles and retrofit methods to improve the earthquake resilience of highway bridges irregular span configurations.