Biological weapons date back to the beginnings of recorded history. During the 6th Century B.C., the Assyrians poisoned enemy wells with fungus. During medieval times, it was common for armies to use infected animal carcasses and diseased human corpses to infect opposing armies. As late as 1710, a Russian army besieging a Swedish city catapulted plague-infected corpses over the city walls. Evidence exists that biological warfare was used against various indigenous Native American tribes in the 1700's. However, deliberate large-scale production and weaponization of biological weapons did not start in earnest until the 20th century.

During the Sino-Japanese War, beginning in 1937 and extending into World War II, the notorious Unit 731 of the Imperial Japanese Army experimented with various biological weapons on thousands of human subjects. Chinese military prisoners were deliberately infected with agents such as anthrax, plague, and cholera, and as many as eleven Chinese cities were attacked with plague-infected fleas. Several hundred thousand Chinese were victims of these attacks, as well as 1,700 Japanese troops who were accidentally infected in a 1941 attack.

In 1942, the United States began an offensive biological weapons program at then Camp Detrick in Maryland where testing with anthrax and other pathogens commenced. The program continued until 1969 when President Nixon ended the development of offensive biological weapons. The defensive research program continues to this day at (now) Fort Detrick with the United States Army Medical Research Institute of Infectious Diseases (USAMRIID).

The British, likewise, began a testing program during World War II amid fears that Germany might attack the United Kingdom with biological or chemical weapons. As part of an early bioweapons test, they released anthrax spores on the Scottish island Gruinard in 1942 and wiped out a flock of sheep. The island, itself, remained contaminated until it was disinfected in 1968 with 280 tons of formaldehyde and the removal of hundreds of tons of topsoil. Like the US, the UK maintains a defensive bioweapons research program at its Porton Down research facility.