He was the son of theologian Michael Walther the Younger (1638–1692).

At Leipzig he became a professor of anatomy (1728), pathology (1732) and therapy (1737).

In 1730 he became director of the Leipzig Botanical Gardens, and in 1737 was rector at the university.

Among his numerous writings was a 1735 botanical treatise called Designatio plantarum quas hortus AF Waltheri complectitur, in which he provides descriptions of thousands of plant species from his private botanical garden.

As a physician he made contributions in the fields of myology and angiology, and has several medical and anatomical terms named after him, including: The plant genus Waltheria from the family Sterculiaceae is named after him.