Anthropogenic disturbances have been widely documented to affect organic matter (OM) sources in lakes; however, most studies have revealed the unreliability of estimating ecological changes from a single or a few sediment cores within a single lake. Here, we combined multi-core analyses, including total organic carbon and total nitrogen contents and their stable carbon and nitrogen isotope ratios (δ¹³C_org and δ¹⁵N, respectively) with a Bayesian isotope mixing model to track the origins of OM and characterize the environmental changes in Lake Yangzong, a plateau lake located in the Yunnan Plateau, Southwest China. The results showed that allochthonous OM (C3 plants: 31.2–78.3%; soil OM: 4.4–26.6%) was the dominant sediment OM source, and the contributions of plankton, soil OM, and sewage decreased from the south to the north. The temporal increase in δ¹⁵N might have indicated an increase in nitrogen discharge caused by human activities, whereas the variation of δ¹³C_org was mainly controlled by allochthonous sources. Further analysis showed that there were significant differences in the lake environment evolution at different sites from the 1950s in response to anthropogenic disturbances. For example, there was a significant shift in the lake environment at the southern site (S1) from the 1990s, whereas a rapid environmental change was documented at the middle site (S2) over the past half-century. Rapid environmental fluctuation occurred at the northern site (S3) owing to soot air pollution occurring on the north shore of the lake from 1970 to 1990. These findings reveal the spatiotemporal characteristics of ecological changes and highlight the sensitivity of the deep-water area of deep lakes to anthropogenic disturbances.