The Ile River is the main water artery of the Lake Balkhash basin and the main fresh water resource supplying the south-eastern part of Kazakhstan. Increasing human economic activity makes it necessary to assess the anthropogenic load of the river on various ecosystems, including possible harmful effects. The assessment of anthropogenic load on the Ile River ecosystem was realized by the anthropogenic load fraction indicator and by the values of the chemical substance inflow modulus. For this purpose, the Ile River was divided into 3 sections: section I—from the border post HP Dobyn to 164 km above Kapshagai hydroelectric power plant (HPP); section II—between the points 164 km above and 37 km below Kapshagai HPP; and section III —from 37 km below HPP to Ushzharma village. The anthropogenic load strongly depends on the share of anthropogenic impact contributed by pollutants. Characteristic pollution components are copper, and in some cases zinc, ammonium, and nitrite nitrogen. The assessment of anthropogenic load also considers organic and biogenic substances in the chemical composition of river water. The variability in the volume of dissolved chemical inflows in different sections of the river made it possible to assess the transformation of anthropogenic load along the length of the Ile River.