The Arvandroud river (also known as Shatt-al-Arab) and its estuary have been degraded due to the changing river flow regime in the Tigris and Euphrates. This study assessed changes in flow from the major rivers and the impacts on the estuary. To assess the river flow changes, three major flow regime attributes were computed: timing (TIF), magnitude (MIF), and variability (VIF). By combining these indices, the total flow regime impact factor (IF) was scaled between 0 and 1, and classified into five groups: Low (0.80<IF<1.0), Incipient (0.60<IF<0.80), Moderate (0.40<IF<0.60), Severe (0.2<IF<0.40), and Drastic (0.0<IF<0.20). Flow regime impact maps were then created for 1941–1955, 1960–1970, 1975–1984, and 1990–2000. These revealed that, over time, the impact has extended along the basin from downstream to upstream, with a significant flow regime change from 1941–1955 to 1990–2000 in the Tigris, Euphrates, and Arvandroud. Analysis of remote sensing data revealed that the change in the flow regime has led to land degradation in the Arvandroud estuary during the past 46 years (1972–2018). In addition, the impact of the Iran–Iraq war (based on degradation of vegetation cover between 1985 and 1988) is 5.1 times of mean rate of change during 1972–2018. This study thus contributes new information on estuaries and the impact of upstream land and water use change.