Schiff, the son of a merchant from Frankfurt am Main, obtained his doctorate from the University of Göttingen in 1844. After working in the Frankfurt Zoological Museum, Schiff moved to Bern in 1854 as professor of comparative anatomy where he remained until 1863 when he was appointed to the chair of physiology in Florence. A campaign against vivisection forced Schiff to leave Florence in 1876 when he accepted the professorship of physiology at Geneva.

In 1856 Schiff demonstrated that removal of the thyroid gland in dogs and guinea pigs resulted in their death. He also showed, in 1885, that the effect could be postponed by grafting a piece of the gland elsewhere in the animal before its removal. The relief was however only temporary as the gland was absorbed by the body. Unfortunately Schiff's earlier work was unknown to surgeons like Theodor Kocher when, in the early 1870s, they began to perform thyroidectomies in humans, operations that often led to tragic ends.

Schiff had also worked in the 1850s on nervous control of the blood supply. By cutting the brainstem he was able to show the existence of special centers in the brain for the control of vasomotor nerves, nerves that narrow or widen blood vessels as the body's demand rises and falls. The same results were independently obtained by Claude Bernard.