We used a 26Al-10Be burial isochron method to date the glacial stratigraphic section in Missouri, USA, that records the largest advances of the Laurentide Ice Sheet. This permits an improved comparison of terrestrial and marine records of glaciation. The first recorded advance of the Laurentide Ice Sheet reached 39°N, near the extreme southern limit of North American glaciation, 2.4 Ma. The next advance to this latitude took place near the beginning of the mid-Pleistocene transition, 1.3 Ma, and three more took place from 0.75 to 0.2 Ma. There is no evidence that the Laurentide Ice Sheet advanced south of ∼45°–47°N between 2.4 and 1.3 Ma. This chronology: (1) shows that North American continental glaciation postdated Cordilleran alpine glaciation; (2) is consistent with the hypothesis that both of these events were threshold responses to tropical cooling; (3) is consistent with the hypothesis that the first advance of the Laurentide Ice Sheet was glaciologically anomalous due to the presence of deformable preglacial regolith; (4) is not consistent with the hypothesis that this deformable regolith persisted until the mid-Pleistocene transition; and (5) indicates that the increase in global ice volume at the mid-Pleistocene transition was at least in part the result of a more extensive Laurentide Ice Sheet.