Fries received his Ph.D. from the University of Lund in 1811 and was appointed as a science lecturer there. Later he was appointed professor and demonstrator in botany but left to accept a professorship at the University of Uppsala, from which he retired in 1859 to study fungi.

During his stay at Lund, Fries had begun to collect and describe known species for his Systema Mycologicum, 3 vol. (1821–32), in which he introduced a new system for classifying fungi. With the exception of a few changes with respect to microscopic discoveries, the system is still valid for many groups of fungi today.

Fries also developed a system for classifying lichens based on the characters of their fruiting bodies (the organs that produce reproductive spores). This system, presented in his Lichenographia Europaea Reformata (1831), was widely accepted until the use of the microscope revolutionized knowledge in this field. Fries was the first person to distinguish between lichens with external coverings on the fruiting body and those without.