Major changes in the Holocene were identified based on a diatom and geochemical analysis of sediment cores from Lakes Ufimskoe and Syrytkul (the Southern Urals). The Lake Ufimskoe ecosystem in the Central mountain area is identified to be highly sensitive to variations in temperature. Meanwhile, Lake Syrytkul is more responsive to climate aridization because of its limnological characteristics and less precipitation in the piedmont area. Climate events were the main drivers for lake ecosystems dynamics throughout almost the whole history of the lakes. The records of lake sediments reflect several climate events noted elsewhere in the Northern Hemisphere: Lateglacial–Holocene transition (~12,000–11,600), Preboreal oscillation (~11,200–11,000 cal. BP), climate warming and aridization (~9700–9600 cal. BP), warming and increase in precipitation since 9000 cal. BP, climate aridization at ~5800 cal. BP, cooling since 4000 cal. BP, and warming at ~2500 cal. BP. Climate warming of the last hundred years was not reflected in lake sediment records because of the significant human impact on the lake ecosystem. The upper sediments of both lakes are enriched in As, Bi, Sb, Te, Sn, Cd, Cu, Zn and Pb because of the influence of the Karabash copper smelter. However, the significant changes of the Lake Syrytkul ecosystem are not related to the technogenic impact and explained mainly by the dam construction. The changes in diatom communities identified in Lake Ufimskoe, which is located in an area geologically sensitive to acidification, are related to the acidification and heavy metal loading on the water area.