Hedwig studied medicine at the University of Leipzig but took up botany when the city of Kronstadt refused to grant him a license to practice medicine. In 1781 he returned to Leipzig and became professor of medicine in 1786 and of botany in 1789. Meanwhile, he had begun a study of the mosses and produced Fundamentum Historiae Naturalis Muscorum Frondosorum, 2 vol. (1782–83; “Elements of the Natural History of Leafy Mosses”), in which he dealt with the anatomy, fertilization, and reproduction of mosses and introduced a new method of classification based on the distribution of spores (reproductive bodies). Hedwig was the first to recognize the true organs of reproduction in mosses. Skilled in the use of the microscope, he identified more mosses than any other botanist of his time and produced a series of well-illustrated, informative books on them.

At his death, Hedwig was working on his most important contribution, Species Muscorum Frondosorum (1801; “Species of Leafy Mosses”), which became the official basis for the nomenclature of the mosses.