The contrasting outcomes of tumor promotion or cellular senescence have both been ascribed to increased levels of reactive oxygen species (ROS). Instead, I demonstrate that endogenous expression of K-Ras^G12D in primary murine cells and tissues unexpectedly triggers a reduction of ROS due to the activation of an antioxidant program by the Nrf2 transcription factor. Persistent Nrf2 activation maintains the decreased intracellular redox state and promotes hyperproliferation of K-Ras^G12D expressing cells, and this occurs through engagement of the mitogen activated protein kinase (MAPK) Ras effector pathway. These findings are not shared by cells ectopically overexpressing oncogenic Ras, where transient induction of Nrf2, ROS production and cellular senescence are instead observed. Nrf2 is activated in human and mouse pancreatic cancer, and Nrf2 deficiency or glutathione depletion both impair K-Ras^G12D – dependent cellular proliferation and carcinogenesis in vivo. Therefore, decreased ROS can promote carcinogenesis, presenting new opportunities to treat and prevent K-Ras mutant cancers.