Anti-vaccine activism, which collectively constitutes the "anti-vax" movement, is a set of organized activities expressing opposition to vaccination. These collaborating networks often seek to increase vaccine hesitancy by disseminating vaccine misinformation and disinformation. As a social movement, it employs tools ranging from traditional news media to various forms of online communication. Activists have primarily—though not exclusively—focused on opposing childhood vaccination, and have sought to expand their influence from niche subgroups into national political debates.

Ideas that later coalesced into anti-vaccine activism predate vaccines themselves. The movement, along with fringe doctors, has propagated various myths and conspiracy theories, alongside misinformation and disinformation. These efforts have significantly increased vaccine hesitancy and influenced public policy regarding the ethical, legal, and medical aspects of vaccination. In contrast, there is no substantive debate or hesitancy within mainstream medical circles about the benefits of vaccination; the scientific consensus is "clear and unambiguous" in favor of vaccines. Despite this consensus, the anti-vaccine movement has been partially successful in distorting the public understanding of science in popular culture.

Ideas that would eventually coalesce into anti-vaccine activism have existed for longer than vaccines themselves. Some philosophical approaches (e.g. homeopathy, vitalism) are incompatible with the microbiological paradigm that explains how the immune system and vaccines work. Vaccine hesitancy and anti-vaccine activism exist within a broader context that involves cultural tradition, religious belief, approaches to health and disease, and political affiliation.

Opposition to variolation for smallpox (a predecessor to vaccination) was organized as early as the 1720s around the premise that vaccination was unnatural and an attempt to thwart divine judgment. Religious arguments against inoculation, the earliest arguments against vaccination, were soon advanced. For example, in a 1722 sermon entitled "The Dangerous and Sinful Practice of Inoculation", the English theologian Reverend Edmund Massey argued that diseases are sent by God to punish sin and that any attempt to prevent smallpox via inoculation is a "diabolical operation". It was customary at the time for popular preachers to publish sermons, which reached a wide audience. This was the case with Massey, whose sermon reached North America, where there was early religious opposition, particularly by John Williams. A greater source of opposition there was William Douglass, a medical graduate of Edinburgh University and a Fellow of the Royal Society, who had settled in Boston.

Vaccination itself was invented by British physician Edward Jenner, who published his findings on the efficacy of the practice for smallpox in 1798. By 1801, the practice had been widely endorsed in the scientific community, and by several world leaders. Philadelphia physician John Redman Coxe, noting that even then false accounts were circulated of negative effects of vaccination, wrote,

"Such are the falsehoods which impede the progress of the brightest discovery which has ever been made! But the contest is in vain! Time has drawn aside the veil which obstructed our knowledge of this invaluable blessing; and in the examples of the Emperor of Constantinople, of the Dowager Empress of Russia, and the King of Spain, we may date the downfall of further opposition."

Coxe's expectation of an end to opposition to vaccination proved premature, and through much of the nineteenth century, the principles, practices and impact of vaccination were matters of active scientific debate. The principles behind vaccination were not clearly understood until the end of the nineteenth century. The importance of hygiene in the preparation, storage, and administration of vaccines was not always understood or practiced. Reliable statistics on vaccine efficacy and side effects were difficult to obtain before the 1930s.

In the United Kingdom, the Vaccination Act 1853 (16 & 17 Vict. c. 100) required that every child be vaccinated within three or four months of birth. It set a precedent for the state regulation of physical bodies, and was fiercely resisted. The following year, in 1854, John Gibbs published the first anti-compulsory-vaccination pamphlet, Our Medical Liberties. By the 1860s, anti-vaccinationism in Britain was active in the working class, labor aristocracy, and lower middle class. It had become associated with alternative medicine and was part of a larger culture of social and political dissent that included both labor unions and religious dissenters.