Thanks to the availability of connectome data that map connectivity between multiple brain areas, it is now possible to build models of whole-brain activity. At the same time, advances in mean-field techniques have led to biologically based population models that integrate biophysical features such as membrane conductances or synaptic conductances. In this paper, we show that this approach can be used in brain-wide models of mice, macaques, and humans.We illustrate this approach by showing the transition from wakefulness to sleep, simulated using multi-scale models, in the three species. We compare the level of synchrony between the three species and find that the mouse brain displays a higher overall synchrony of slow waves compared to monkey and human brains. We show that these differences are due to the different delays in axonal signal propagation between regions associated with brain size differences between the species. We also make the program code—which provides a set of open-source tools for simulating large-scale activity in the cerebral cortex of mice, monkeys, and humans—publicly available.