Understanding what cranial shape, or cranial morphology, can tell us about the history of populations is an important question in anthropology, and has been very important in the discussion about the Settlement of the Americas. This research article explores the causes of cranial differences of pre-historic Mexican populations, comparing them to samples spread out across North America, Central America, and South America, as well as from East Asia and Australo-Melanesia. The analysis show that the populations can be divided in two distinct biological groups: one including East Asian, Native American, and South American coastline populations; the other including Australo-Melanesian and the Paleoamerican series. Most interestingly, the Mexican populations show relatively large degrees of differences, despite being geographically and chronologically close to each other. These results support some of our previous findings, but also suggests that physical barriers (mountains, large bodies of water, etc.) as well as social barriers (cultural and linguistic differences) can cause important differentiation in smaller regions of the planet. For us, knowing that there are situations where you can have this wider variation in cranial shape present in smaller geographic areas highlights how complex the process of occupation of the Americas was.