He studied at the college of Neuchâtel and in Berlin,Germany, where he began a lifelong friendship with Louis Agassiz. He was professor of history and physical geography at the short-lived Neuchâtel Academy from 1839 to 1848, when he removed, at Agassiz's instance, to the United States, settling in Cambridge, Massachusetts. For several years he was a lecturer for the Massachusetts State Board of Education, and he was professor of geology and physical geography at Princeton from 1854 until death. Today, the building housing the Department of Geosciences at Princeton is named Guyot Hall in his honor.
He ranked high as a geologist and meteorologist. As early as 1838, he undertook, at Agassiz's suggestion, the study of glaciers, and was the first to announce, in a paper submitted to the Geological Society of France, certain important observations relating to glacial motion and structure. Among other things he noted the more rapid flow of the center than of the sides, and the more rapid flow of the top than of the bottom of glaciers; described the laminated or ribboned structure of the glacial ice, and ascribed the movement of glaciers to a gradual molecular displacement rather than to a sliding of the ice mass as held by de Saussure. He subsequently collected important data concerning erratic boulders.
His extensive meteorological observations in America led to the establishment of the United States Weather Bureau, and his Meteorological and Physical Tables (1852, revised ed. 1884) were long standard. His graded series of text-books and wall-maps were important aids in the extension and popularization of geological study in America. In addition to text-books, his principal publications were: