Born in Woodstock, Vermont, he graduated from Dartmouth College in 1820, was admitted to the bar in 1825, and practised law in Burlington, Vermont; he also devoted himself to philological studies. In 1835 he was appointed to the Supreme Executive Council of Vermont, and from 1843 to 1849 was a Whig representative in Congress. In 1849 he was appointed United States minister resident in Turkey, and in 1852-1853 discharged a mission to Greece in connection with the imprisonment of an American missionary, Dr. Jonas King (1792-1869). He returned to Vermont in 1854, and in 1857 was a member of the state railway commission. In 1861 he became the first United States minister to the kingdom of Italy, and died in that office at Vallombrosa. He was buried in the Protestant cemetery in Rome.

Marsh was an able linguist, able to both speak and write fluently in Scandinavian and half a dozen other European languages. He was a remarkable philologist for his day, and a scholar of great breadth, knowing much of military science, engraving and physics, as well as Icelandic, which was his specialty. He wrote many articles for Johnson's Universal Cyclopaedia, and contributed many reviews and letters to the Nation. His chief published works are:

A Compendious Grammar of the Old Northern or Icelandic Language (1838), compiled and translated from the grammars of Rask The Camel, his Organization, Habits, and Uses, with Reference to his Introduction into the United States (1856) Lectures on the English Language (1860) The Origin and History of the English Language (1862; revised ed., 1885) Man and Nature (1865) The last-named work was translated into Italian in 1872, and, largely rewritten, was issued in 1874 under the title The Earth as Modified by Human Action; a revised edition was published in 1885. He also published a work on Mediaeval and Modern Saints and Miracles (1876).

Man and Nature constituted an early work of ecology, and played a role in the creation of the Adirondack State Park. Marsh argued that deforestation could lead to desertification. Referring to the clearing of once-lush lands surrounding the Mediterranean, he asserted "the operation of causes set in action by man has brought the face of the earth to a desolation almost as complete as that of the moon."

His second wife, Caroline (Crane) Marsh (1816-1901), whom he married in 1839, published Wolfe of the Knoll and other Poems (1860), and the Life and Letters of George Perkins Marsh (New York, 1888). This last work was left incomplete, the second volume never having been published. She also translated from the German of Johann C. Biernatzki (1795-1840), The Hallig; or the Sheepfold in the Waters (1856). (See "Hallig").