The ESHG was established on March 15, 1967 by a small group of outstanding European Geneticists  (European Journal of Human Genetics: 3, 63-64, 1995).  The decision which led to the founding of the ESHG was taken at an informal meeting of European participants at the IIIrd International Congress of Human Genetics in Chicago in September 1966. Membership was open; the first annual membership fee was $6.  The founding chairman was J. Mohr who was secretary-general of the society until 1991. Contact with the members was kept through a Bulletin.

The first symposium of the new society was held in Copenhagen on 18-19 November 1967. The invited lectures were on Genetic polymorphism in man, and there was a session for contributed papers.

In 1991 the Statutes were redrafted to give the society a new momentum and further modifications were added in 1996 when the society also became an International Association under Belgian Law. In the mean time the society grew from a few hundred to over 1000 members. In 1993 the society published its own Journal, The European Journal of Human Genetics, which moved from 4 to 6 to 8 issues per year and now appears  monthly.

In 1996 the ESHG together with the American  Society of Human Genetics  and the Human Genetics Society of Australasia  founded the International Federation of Human Genetic societies, which represents a growing number of national societies and which will organise its first International meeting in Vienna in 2001.

In 2020 the society was moved to Vienna and registered under Austrian Law. It currently has around 3,500 members.

The ESHG is in regular contact with different directorates of the EU commission and other scientific organisations. With the support of the ESHG, the European Alliance of Genetic support groups was founded in 1991 in Leuven.

The society has a partnership with some major diagnostic biotech companies to keep abreast of all the complex issues related to human genetics.