Defining mechanisms that maintain tissue stem cells during homeostasis, stress, and aging is important for improving tissue regeneration and repair and enhancing cancer therapies. Here, we show that Id1 is induced in hematopoietic stem cells (HSCs) by cytokines that promote HSC proliferation and differentiation, suggesting that it functions in stress hematopoiesis. Genetic ablation of Id1 increases HSC self-renewal in serial bone marrow transplantation (BMT) assays, correlating with decreases in HSC proliferation, mitochondrial biogenesis, and reactive oxygen species (ROS) production. Id1−/− HSCs have a quiescent molecular signature and harbor less DNA damage than control HSCs. Cytokines produced in the hematopoietic microenvironment after γ-irradiation induce Id1 expression. Id1−/− HSCs display a blunted proliferative response to such cytokines and other inducers of chronic proliferation including genotoxic and inflammatory stress and aging, protecting them from chronic stress and exhaustion. Thus, targeting Id1 may be therapeutically useful for improving HSC survival and function during BMT, chronic stress, and aging. Display omitted •Id1−/− HSCs have enhanced self-renewal potential and are maintained during BMT•Id1−/− HSCs show reduced oxidative stress and increased quiescence after BMT•Id1−/− HSCs are protected from inflammatory cytokine-induced proliferative stress•Id1−/− HSCs are protected from exhaustion by chronic inflammatory stress and aging Singh et al. show that Id1 is an important mediator of stress hematopoiesis. They found that Id1 deletion protects HSCs from exhaustion in multiple paradigms of chronic and physiologically relevant stress and promotes their quiescence, suggesting that targeting Id1 may improve HSC survival and function during chronic stress and aging.