Inland waterways are vital to the Nation’s economic strength, and to the health and welfare of the American people. This paper describes an end-to-end systems analysis methodology for inland waterways that incorporates infrastructure interdependencies and cascading impacts due to loss of a key asset. The methodology leverages available Federal, State, and private-sector data, methods, tools, expertise, and existing studies to minimize duplication and ensure broad acceptance and applicability. The approach determined potential adverse scenarios and impacts upon directly affected assets (e.g., downtime of a lock, dam, or bridge), and identified industrial sites that would be affected by the loss of normal transport capability (e.g., loss of barge transport). Origin and destination information along an inland waterway was correlated with the port and dock locations of industrial sites. Practical alternative transportation modes and routes for each affected industrial site were identified, based on existing railheads and estimated alternative mode system surge capacity. Reasonable assumptions were developed and applied where specific data were unavailable, and consequences such as additional transportation costs, costs of transportation delays, jobs losses, and economic impacts on other sectors locally and regionally were determined for unique inland waterway facilities critical to the Illinois Waterway.