Key PointsQuestionWhat is the association of low-level arsenic exposure with brain structure and function and subsequent cognitive functioning?FindingsThis cohort study of 1014 participants describes a syndrome of impairments in executive function associated with low-level arsenic exposure and characterizes its underlying brain mechanisms. The arsenic-associated impairments are exacerbated by risk factors such as poor nutrition and poverty.MeaningThese findings call for a reexamination of the definitions of safe levels of environmental arsenic exposure; improvements in nutrition and socioeconomic conditions may additionally serve as potential mechanisms to ameliorate the harmful consequences of environmental arsenic insults.