The Aral Sea stands as a stark illustration of how an inland sea-lake can vanish as a result of unsustainable economic exploitation of natural water resources. The sea’s deterioration caused permanent alterations to its ecosystem, the loss of formerly abundant valuable fish species, and other devastating outcomes. This analysis examines the history and current condition of the Aral Sea, the species composition prior to its desiccation phase, and the transformations of its biota under human influence. Given that water salinity is a primary environmental factor affecting aquatic life, the sharp increase in the Aral Sea’s salinity represents the most significant environmental impact. The reduction in the sea’s area and volume has been paralleled by a steady rise in salinity levels. From 1960, salinity climbed from typical levels of 10–12‰ to nearly 140‰ by 2018. Most aquatic organisms that lived in the Aral Sea before the salinization process have vanished from the basin. Fish populations, benthic invertebrates (macrozoobenthos), zooplankton, and macroalgae communities were severely affected. Shifts in species composition—both naturally occurring and human induced—are reviewed across three phases: before salinization, during the salinization period, and after the division of the Aral Sea basin.