The middle reaches of the Minjiang River, shaped by the Dujiangyan irrigation system, provide a typical setting for studying long-term human–water interactions. During the Little Ice Age, the water management system as a whole experienced a full cycle of recovery, expansion, and decline from 1644 to 1949 (Qing to Republican period), although subregions exhibited marked spatial heterogeneity. This heterogeneity makes the area an ideal case for comparative analysis; however, previous studies have neither quantitatively reconstructed river–canal changes nor systematically disentangled the composite natural and anthropogenic drivers across different subregions. Using archival documents, historical maps, remote sensing imagery, and water cultural heritage sites, this study reconstructs the evolution and quantifies two change types: anthropogenic construction, including new construction, reconstruction, and modification, and environmentally driven changes such as rerouting, damage, and maintenance. Correlations were analyzed among the four subregions: Inner River, Outer River, Nanhe River, and the Lower Basin to identify driving mechanisms. Results indicate that anthropogenic construction is constrained by natural conditions and driven by population growth, whereas environmentally driven changes are primarily caused by floods and worsened by canal head maintenance failure. The four spatially differentiated driving patterns are: Inner River—human-dominated intervention type; Outer River—flood stress type; Nanhe River—low-disturbance stable type; and Lower Basin—natural–human composite type. This study offers new insights into long-term human–water interactions in large irrigation districts under climate change.