This dissertation develops mathematical models to efficiently manage the inland waterway port operations while minimizing the overall supply chain cost. In the first part, a capacitated, multi-commodity, multi-period mixed-integer linear programming model is proposed capturing diversified inland waterway transportation network related properties. We developed an accelerated Benders decomposition algorithm to solve this challenging NP-hard problem. The next study develops a two-stage stochastic mixed-integer nonlinear programming model to manage congestion in an inland waterway transportation network under stochastic commodity supply and water-level fluctuation scenarios. The model also jointly optimizes trip-wise towboat and barge assignment decisions and different supply chain decisions (e.g., inventory management, transportation decisions) in such a way that the overall system cost can be minimized. We develop a parallelized hybrid decomposition algorithm, combining Constraint Generation algorithm, Sample Average Approximation (SAA), and an enhanced variant of the L-shaped algorithm, to effectively solve our proposed optimization model in a timely fashion. While the first two parts develop models from the supply chain network design viewpoint, the next two parts propose mathematical models to emphasize the port and waterway transportation related operations. Two two-stage, stochastic, mixed-integer linear programming (MILP) models are proposed under stochastic commodity supply and water level fluctuations scenarios. The last one puts the specific focus in modeling perishable inventories. To solve the third model we propose to develop a highly customized parallelized hybrid decomposition algorithm that combines SAA with an enhanced Progressive Hedging and Nested Decomposition algorithm. Similarly, to solve the last mathematical model we propose a hybrid decomposition algorithm combining the enhanced Benders decomposition algorithm and SAA to solve the large size of test instances of this complex, NP-hard problem. Both proposed approaches are highly efficient in solving the real-life test instances of the model to desired quality within a reasonable time frame. All the four developed models are validated a real-life case study focusing on the inland waterway transportation network along the Mississippi River. A number of managerial insights are drawn for different key input parameters that impact port operations. These insights will essentially help decisions makers to effectively and efficiently manage an inland waterway-based transportation network.