Arsenic compounds have been known since ancient times, with the word "arsenic" originating from the Greek word arsenikon, meaning "yellow orpiment". The element itself was possibly first observed in the 13th century by Albertus Magnus, who noted a metal-like substance when heating the mineral arsenicum.

In the 17th-19th centuries, arsenic was frequently used for murder due to the lack of specific symptoms and the difficulty in detecting it. It became known as the "poison of kings" and the "king of poisons". Arsenic was also used in the Victorian era by women to improve their complexion, leading to accidental poisonings.

Arsenic compounds began to be used in agriculture as insecticides, herbicides and wood preservatives in the late 19th century. In 1900, Paul Ehrlich developed the first effective arsenic-based drug, Salvarsan, to treat syphilis. Arsenic was also used as a war gas called Lewisite during WWII, leading to the development of the antidote British Anti-Lewisite (BAL).

Today, arsenic is still used in some pesticides and wood preservatives, but its use has declined due to toxicity concerns. The element itself is produced by heating arsenopyrite ore in the absence of air. While arsenic has a long history of use, its toxicity has also made it notorious as a deadly poison throughout the centuries.