Human neuroimaging studies have demonstrated that brain development progresses hierarchically along an S–A axis in which areas of association cortex are the last to mature.Animal models delineate a hierarchical progression of critical periods of elevated experience-dependent plasticity across sensory systems which is governed by a conserved set of neurobiological mechanisms.We propose that hierarchical development along the S–A axis in humans is driven by a cascade of critical periods that culminate in association cortices during adolescence.We highlight advances in in vivo neuroimaging and computational approaches, including pharmacological functional magnetic resonance imaging (fMRI), chemogenetic fMRI, and biophysical modeling, that can provide insights into the development of critical period mechanisms along the S–A axis in humans. To understand human brain development it is necessary to describe not only the spatiotemporal patterns of neurodevelopment but also the neurobiological mechanisms that underlie them. Human neuroimaging studies have provided evidence for a hierarchical sensorimotor-to-association (S–A) axis of cortical neurodevelopment. Understanding the biological mechanisms that underlie this program of development using traditional neuroimaging approaches has been challenging. Animal models have been used to identify periods of enhanced experience-dependent plasticity – 'critical periods' – that progress along cortical hierarchies and are governed by a conserved set of neurobiological mechanisms that promote and then restrict plasticity. In this review we hypothesize that the S–A axis of cortical development in humans is partly driven by the cascading maturation of critical period plasticity mechanisms. We then describe how recent advances in in vivo neuroimaging approaches provide a promising path toward testing this hypothesis by linking signals derived from non-invasive imaging to critical period mechanisms. To understand human brain development it is necessary to describe not only the spatiotemporal patterns of neurodevelopment but also the neurobiological mechanisms that underlie them. Human neuroimaging studies have provided evidence for a hierarchical sensorimotor-to-association (S–A) axis of cortical neurodevelopment. Understanding the biological mechanisms that underlie this program of development using traditional neuroimaging approaches has been challenging. Animal models have been used to identify periods of enhanced experience-dependent plasticity – 'critical periods' – that progress along cortical hierarchies and are governed by a conserved set of neurobiological mechanisms that promote and then restrict plasticity. In this review we hypothesize that the S–A axis of cortical development in humans is partly driven by the cascading maturation of critical period plasticity mechanisms. We then describe how recent advances in in vivo neuroimaging approaches provide a promising path toward testing this hypothesis by linking signals derived from non-invasive imaging to critical period mechanisms.