Abstract DNA methylation is environment-sensitive and can mediate stress responses. In long-lived trees, changing environments might cumulatively shape the methylome landscape over their lifetime. However, because high-resolution methylome studies usually focus on single environmental cues, it remains unclear to what extent the methylation responses are generic or stress-specific, and how this relates to their long-term stability. Here, we studied the methylome plasticity of a Populus nigra cv. ‘Italica’ clone that is widespread across Europe. Adult trees from a variety of geographic locations were clonally propagated in a common garden experiment, and the ramets were exposed to cold, heat, drought, herbivory, rust infection, and salicylic acid treatments. Through comprehensive whole-genome bisulfite sequencing, we analyzed stress-induced and naturally occurring DNA methylation variants. Stress-induced methylation changes predominantly targeted transposable elements. When occurring in CG/CHG contexts, the same regions were often affected by multiple stresses, suggesting a generic response of the methylome. Drought stress caused a distinct CHH hypermethylation response in transposable elements, affecting entire TE superfamilies near drought-responsive genes. Methylation differences in CG/CHG contexts that were induced by stress treatments showed striking overlap with methylation differences observed between trees from distinct geographical locations. Thus, we revealed genomic hotspots of methylation change that are not stress-specific and that contribute to natural DNA methylation variation, and we identified specific transposable element superfamilies that respond to a specific stress with possible functional consequences. Our results underscore the importance of studying the effects of multiple stressors in a single experiment for recognizing general versus stress-specific methylome responses.