The present-day shape, form, and surficial features, and the future directional movement and changes of the morphometry of any large river ecosystem and its interface zones are the results of all the natural and human interventions on the system for the last several decades to centuries. Almost all watersheds of all major rivers of the world have already been subjected to intense pressures from agriculture, urban sprawl, water supplies, transportation, and recreation. Two of the major rivers of the United States have also experienced these major constraints, and they have responded with changes in their morphometry and riverine environments. Specific examples are Pool 19 of the Mississippi River, which extends about 74 kilometers (km), and the Peoria Lake on the Illinois River, which extends about 16 km. Both of these river reaches have been altered by the construction of locks and dams and also serve as the sinks and transient conduits for the sediments and other solid matters produced on and delivered from their altered watersheds. The present-day Pool 19 was created when a lock and dam were constructed in 1913 on the Mississippi River near Keokuk, Iowa. Since then, this pool has lost about 68% of its 1903 capacity, with annual sediment deposition of 3.3 million metric tons. Consequently, the lower portion of this pool has been undergoing a transformation from a riverine to a lacustrine to a palustrine and then to a terrestrial environment. Research has shown that this transition may be final by the years 2030 to 2050. Both hydrologic and man-made activities are responsible for this change. On the other hand, the fate of Peoria Lake in the Illinois River is much more ominous: the conversion from riverine to lacustrine, palustrine, and then terrestrial environments may take place even more quickly. Many other large rivers of the world may well face similar fates as a result of past and ongoing hydraulic, hydrologic, and human activities. This paper demonstrates this premise through a series of examples, citing research conducted over the last several decades.