Communication between gray matter regions underpins all facets of brain function. To date, progress in understanding large-scale neural communication has been hampered by the inability of current neuroimaging techniques to track signaling at whole-brain, high-spatiotemporal resolution. Here, we use 2.77 million intracranial EEG recordings, acquired following 29,055 single-pulse electrical stimulations in a total of 550 individuals, to study inter-areal communication in the human brain. We found that network communication models—computed on structural connectivity inferred from diffusion MRI—can explain the propagation of direct, focal electrical stimulation through white matter, measured at millisecond time scales. Building on this finding, we show that a parsimonious statistical model comprising structural, functional and spatial factors can accurately and robustly predict cortex-wide effects of brain stimulation (out-of-sample R 2 =54%). Our work contributes towards the biological validation of concepts in network neuroscience and provides insight into how white matter connectivity shapes inter-areal signaling. We anticipate that our findings will have implications for research on macroscale neural information processing and the design of brain stimulation paradigms.