We show that the human brain contains diverse mitochondrial phenotypes driven by both topology and cell types. Compared with white matter, grey matter contains >50% more mitochondria. Moreover, the mitochondria in grey matter are biochemically optimized for energy transformation, particularly among recently evolved cortical brain regions. Scaling these data to the whole brain, we created a backwards linear regression model that integrates several neuroimaging modalities11 to generate a brain-wide map of mitochondrial distribution and specialization.