Intending to enter the Church, Guyot, who was born at Boudevilliers in Switzerland, studied at the universities of Neuchâtel, Strasbourg, and Berlin, where his interests in science began to absorb him. After teaching in Paris (1835–40) he was appointed professor of history and physical geography at Neuchâtel in 1839 where he remained until 1848, when he emigrated to America. He taught first at the Lowell Technological Institute in Boston before he was appointed, in 1854, to the chair of geology and physical geography at Princeton University.

While in Switzerland he had studied the structure and movement of glaciers, spending much time testing the new theories of Louis Agassiz. In America, under the auspices of the Smithsonian Institution, he began to develop, organize, and equip a number of East Coast meteorological stations. He also surveyed and constructed topographical maps of the Appalachian and Catskill mountains. In 1849 he published his influential work The Earth and Man.