He was born at Femsjö (Hylte Municipality) in Småland as the son of a priest. In 1811 he entered Lund University where he took the doctorate in 1814. In the same year he was appointed to an associate professorship in botany, and in 1824, became a full professor. In 1834 he became Borgström professor (Swed. Borgströmianska professuren, a chair endowed by Eric Erichsson Borgström, 1708 – 1770) in applied economics at Uppsala University. The position was changed to "professor of botany and applied economics" in 1851; he was also the director of the Uppsala University Botanical Garden. In 1821, he was elected an escort for the Royal Swedish Academy of Sciences.

His most important works were the three volume Systema mycologicum (1821 – 1832), Elenchus fungorum (1828), the two volume Monographia hymenomycetum Sueciae (1857 and 1863) and Hymenomycetes Europaei (1874).

Fries is considered to be, after Christian Hendrik Persoon, a founding father of the modern taxonomy of mushrooms. His taxonomy of mushrooms was influenced by Goethe and the German romantics. He utilized spore color and arrangement of the hymenophore (pores, gills, teeth etc.) as major taxonomic characteristics.

When he died, The Times commented: "His very numerous works, especially on fungi and lichens, give him a position as regards those groups of plants only comparable to that of Linnaeus". Fries was succeeded in the Borgström professorship by Johan Erhard Areschoug, after whom Thore Fries, the son of Elias, held the chair.