Human brain size increases dynamically through early development, peaks in adolescence, and varies up to two-fold among adults. But the molecular underpinnings of interindividual variation in brain size remain unknown. Here, we leverage postmortem brain RNA sequencing and estimates of brain size in 2,531 individuals and identified 928 genes that showed genome-wide significant associations. These genes showed distinct neurodevelopmental trajectories and spatial patterns that mapped onto developmental, functional and cellular axes of brain organization. We found that transcriptomic regulation of these genes influences cortical surface area and volume, as well as behavioral traits related to brain function and disease.