Inland waterway transport is an important mode of transportation for many countries and regions. Route planning optimization can reduce navigation time, avoid traffic congestion, and improve transportation efficiency. In actual operations, many vessels determine their navigation routes based on the experience of their shipowners. When the captain fails to obtain accurate information, experience-based routes may pose significant navigation risks and may not consider the overall economic efficiency. This study proposes a comprehensive method for optimizing inland waterway vessel routes using automatic identification system (AIS) data, considering the geographical characteristics of inland waterways and navigation constraints. First, AIS data from vessels in inland waters are collected, and the multi-objective Peak Douglas–Peucker (MPDP) algorithm is applied to compress the trajectory data. Compared to the traditional DP algorithm, the MPDP algorithm reduces the average compression rate by 5.27%, decreases length loss by 0.04%, optimizes Euclidean distance by 50.16%, and improves the mean deviations in heading and speed by 23.53% and 10.86%, respectively. Next, the Ordering Points to Identify the Clustering Structure (OPTICS) algorithm is used to perform cluster analysis on the compressed route points. Compared to the traditional DBSCAN algorithm, the OPTICS algorithm identifies more clusters that are both detailed and hierarchically structured, including some critical waypoints that DBSCAN may overlook. Based on the clustering results, the A* algorithm is used to determine the connectivity between clusters. Finally, the nondominated sorting genetic algorithm II is used to select suitable route points within the connected clusters, optimizing objectives, including path length and route congestion, to form an optimized complete route. Experiments using vessel data from the waters near Shuangshan Island indicate that, when compared to three classic original routes, the proposed method achieves path length optimizations of 4.28%, 1.67%, and 0.24%, respectively, and reduces congestion by 24.15%. These improvements significantly enhance the planning efficiency of inland waterway vessel routes. These findings provide a scientific basis and technical support for inland waterway transport.