Over the last 2 centuries there has been a rapid increase in the proportion of children who grow up in cities. However, relatively little work has explored in detail the physiological and cognitive pathways through which city life may affect early development. To assess this, we observed a cohort of infants growing up in diverse settings across South East England across a 2-day assessment battery. On Visit 1, day-long home recordings were made to monitor infants' physiological stress in real-world settings. On Visit 2, lab batteries were administered to measure infants' cognitive, emotional, and neural reactivity. Infants from more high-density urban environments showed increased physiological stress (decreased parasympathetic nervous system activity) at home. This relationship was independent of socioeconomic status and lifelong stressors. Behaviorally, infants raised in high-density settings showed lower sustained attention in the lab, along with increased behavioral and physiological reactivity during an emotion elicitation task. However, they also showed increased recognition memory for briefly presented stimuli and increased neural engagement with novel stimuli. This pattern is consistent with other research into how elevated physiological stress influences cognition, and with theoretical approaches from adult research that predict that city life is associated with a profile of cognitive strengths as well as weaknesses. Implications for education and developmental psychopathology are discussed.