The modern concept of biological warfare involves the use of biological agents, of which there are pathogens, typically bacteria or viruses, and toxins, which are biologically produced poisons. The history of biological warfare begins in antiquity but was transformed in the 20th century via industrial warfare and advances in microbiology such as genetic engineering.

In the ancient and medieval period, biological warfare commonly overlapped with chemical warfare. This included contamination of food, water, animals, weapons systems, fabrics. In the European Middle Ages, common weapons were poisoned arrows and catapults to launch cadavers or animal corpses. European colonization exposed native populations in the Americas and Australia to smallpox outbreaks, although evidence of successful intentional uses is limited.

In World War I, the German Empire targeted horses and livestock with anthrax and glanders while France used burkholderia. The use of biological weapons in international warfare was theoretically prohibited by the 1925 Geneva Protocol, but research continued, and Japan and the United States did not ratify it until the 1970s. During World War II, many countries initiated large biological weapons programs as part of total war. The Empire of Japan became the first country to use enhanced pathogens. Its Unit 731 and other units, led by Shirō Ishii, dispersed pathogens throughout China during the Second Sino-Japanese War. Plague, cholera, typhoid, anthrax, glanders, and others were used, primarily from air-dropped bomblets filled with infected fleas, a form of entomological warfare. Research was furthered by forced human experimentation on civilians and prisoners of war. The United Kingdom, at Porton Down, and the United States developed advanced biological programs including anthrax bombs.

After the war, an American cover-up gave immunity to biological warfare leaders, from prosecution for Japanese war crimes, in exchange for information to further the United States biological weapons program. Scrutiny during the Vietnam War forced the United States to renounce biological weapons in 1969. This contributed to the 1972 Biological and Toxin Weapons Convention, which comprehensively prohibited their development, production, stockpiling, and use. However, due to its weak inspection measures stemming from the Cold War, an advanced Soviet biological weapons program flourished. Genetic engineering was used to enhance pathogens' climate and antimicrobial resistance. Stockpiled weapons were envisioned for intercontinental attacks against cities, battlefield employment, and anti-agriculture attacks. The 1979 Sverdlovsk anthrax leak, which killed at least 68 people, was the first indication to the world of a continued offensive program.

Ba'athist Iraq also developed a biological weapons program, weaponizing anthrax and toxins, before its disarmament post-Gulf War by the United Nations Special Commission. The unsolved 2001 anthrax attacks in the United States, a week after the September 11 attacks, heightened public fear of biological warfare as a weapon of mass destruction. False allegations by a US-led coalition that Iraq was maintaining its weapons of mass destruction programs played a major role in justifying the 2003 invasion of Iraq.

Antiquity The earliest documented incident of the intention to use biological weapons is possibly recorded in Hittite texts of 1500–1200 BC, in which victims of tularemia were driven into enemy lands, causing an epidemic. Although the Assyrians knew of ergot, a parasitic fungus of rye which produces ergotism when ingested, there is no evidence that they poisoned enemy wells with the fungus, as has been claimed.

According to Homer's epic poems about the legendary Trojan War, the Iliad and the Odyssey, spears and arrows were tipped with poison. During the First Sacred War in Greece, in about 590 BC, Athens and the Amphictionic League poisoned the water supply of the besieged town of Kirrha (near Delphi) with the toxic plant hellebore.Mayor, Andrienne (2003), Greek Fire, Poison Arrows, and Scorpion Bombs: Biological and Chemical Warfare in the Ancient World, The Overlook Press, Peter Mayer Publishers, Inc., , pp 100–101 According to Herodotus, during the 4th century BC Scythian archers dipped their arrow tips into decomposing cadavers of humans and snakes or in blood mixed with manure, supposedly making them contaminated with dangerous bacterial agents like Clostridium perfringens and Clostridium tetani, and snake venom.

In a naval battle against King Eumenes of Pergamon in 184 BC, Hannibal of Carthage had clay pots filled with venomous snakes and instructed his sailors to throw them onto the decks of enemy ships.Rothschild J.H. (1964), Tomorrow's Weapons: Chemical and Biological, New York, New York: McGraw-Hill. The Roman commander Manius Aquillius poisoned the wells of besieged enemy cities in about 130 BC. In about AD 198, the Parthian city of Hatra (near Mosul, Iraq) repulsed the Roman army led by Septimius Severus by hurling clay pots filled with live scorpions at them.Cornelius Nepos, Hannibal 11.5–6. Herodian 3.9.3–8 and Dio Cassius 68.31–75 and Epitome 75.10 and 76.10. Like Scythian archers, Roman soldiers dipped their swords into excrements and cadavers too — victims were commonly infected by tetanus as result.

The use of bees as guided biological weapons was described in Byzantine written sources, such as Tactica of Emperor Leo VI the Wise in the chapter On Naval Warfare.

There are numerous other instances of the use of plant toxins, venoms, and other poisonous substances to create biological weapons in antiquity.

Post-classical ages The Mongol Empire established commercial and political connections between the Eastern and Western areas of the world, through the most mobile army ever seen. The armies, composed of the most rapidly moving travelers who had ever moved between the steppes of East Asia (where bubonic plague was and remains endemic among small rodents), managed to keep the chain of infection without a break until they reached, and infected, peoples and rodents who had never encountered it. The Black Death of the following century, caused by Yersinia pestis strains perhaps spread by Mongol movements, may have killed up to 50 million total — roughly a third of the population of Europe, with unknown casualty counts in the Middle East and North Africa, changing the course of Asian and European history.

Biologicals were extensively used in many parts of Africa from the sixteenth century AD, most of the time in the form of poisoned arrows, or powder spread on the war front as well as poisoning of horses and water supply of the enemy forces. In Borgu, there were specific mixtures to kill, hypnotize, make the enemy bold, and to act as an antidote against the poison of the enemy as well. The creation of biologicals was reserved for a specific and professional class of medicine men. In South Sudan, the people of the Koalit Hills kept their country free of Arab invasions by using tsetse flies as a weapon of war. Several accounts can give an idea of the efficiency of the biologicals. For example, Mockley-Ferryman in 1892 commented on the Dahomean invasion of Borgu, stating that "their (Borgawa) poisoned arrows enabled them to hold their own with the forces of Dahomey notwithstanding the latter's muskets." The same scenario happened to Portuguese raiders in Senegambia when they were defeated by Mali's Gambian forces, and to John Hawkins in Sierra Leone where he lost a number of his men to poisoned arrows.

During the Middle Ages, victims of the bubonic plague were used for biological attacks, often by flinging fomites such as infected corpses and excrement over castle walls using catapults. Bodies would be tied along with cannonballs and shot towards the city area. In 1346, during the siege of Caffa (now Feodossia, Crimea) the attacking Tartar Forces (subjugated by the Mongol Empire under Genghis Khan more than a century earlier), used the bodies of Mongol warriors of the Golden Horde who had died of plague, as weapons. It has been speculated that this operation may have been responsible for the advent of the Black Death in Europe. At the time, the attackers thought that the stench was enough to kill them, though it was the disease that was deadly. (However, in recent years, some scholarship and research has cast doubt on the use of trebuchets to hurl corpses due to factors such as the size of trebuchets and how close they would have to be constructed due to the hilly landscape in Caffa.)

At the siege of Thun-l'Évêque in 1340, during the Hundred Years' War, the attackers catapulted decomposing animals into the besieged area.

In 1422, during the siege of Karlstein Castle in Bohemia, Hussite attackers used catapults to throw dead (but not plague-infected) bodies and 2,000 carriage-loads of dung over the walls.

English Longbowmen usually did not draw their arrows from a quiver; rather, they stuck their arrows into the ground in front of them. This allowed them to nock the arrows faster and the dirt and soil was likely to stick to the arrowheads, thus making the wounds much more likely to become infected.

17th and 18th century Europe The last known incident of using plague corpses for biological warfare may have occurred in 1710, when Russian forces attacked Swedish troops by flinging plague-infected corpses over the city walls of Reval (Tallinn) (although this is disputed). However, during the 1785 siege of La Calle, Tunisian forces flung diseased clothing into the city.

North America

During Pontiac's Rebellion, in June 1763 a group of Native Americans laid siege to British-held Fort Pitt. During a parley in the middle of the siege on June 24, Captain Simeon Ecuyer gave representatives of the besieging Delawares, including Turtleheart, two blankets and a handkerchief enclosed in small metal boxes that had been exposed to smallpox, in an attempt to spread the disease to the besieging Native warriors in order to end the siege.Anderson, Crucible of War, 541–42; Jennings, Empire of Fortune, 447n26. William Trent, the trader turned militia commander who had come up with the plan, sent an invoice to the British colonial authorities in North America indicating that the purpose of giving the blankets was "to Convey the Smallpox to the Indians." The invoice was approved by General Thomas Gage, then serving as Commander-in-Chief, North America. A reported outbreak that began the spring before left as many as one hundred Native Americans dead in Ohio Country from 1763 to 1764. It is not clear whether the smallpox was a result of the Fort Pitt incident or whether the virus was already present among the Delaware people, as outbreaks happened on their own every dozen or so years and the delegates were met again later and seemingly had not contracted smallpox. Trade and combat also provided ample opportunity for transmission of the disease.