Species responses to climate change depend on environment, genetics, and interactions among these factors. Intraspecific cytotype (ploidy level) variation is a common type of genetic variation in many species. However, the importance of intraspecific cytotype variation in determining demography across environments is poorly known. We studied the tree species quaking aspen (Populus tremuloides), which occurs in diploid and triploid cytotypes. This widespread species is experiencing contractions in its western range, which could potentially be linked to cytotype-dependent drought tolerance. We found that interactions between cytotype and environment drive mortality and recruitment across 503 plots in Colorado. Triploids were more vulnerable to mortality relative to diploids and had reduced recruitment on more drought-prone and disturbed plots relative to diploids. Furthermore, there was substantial genotype-dependent variation in demography. Thus, cytotype and genotype variation are associated with decline in this foundation species. Future assessment of demographic responses under climate change will require knowledge of how genetic and environmental mosaics interact to determine species’ ecophysiology and demography.