ESPEN was not formally established until 1980, but its foundations were laid in an informal international meeting in Stockholm in 1979, which has commonly come to be regarded as the first ESPEN meeting.

Here, it was decided to set up a multidisciplinary Society devoted to the study of metabolic problems associated with acute diseases and their nutritional implications and management and to publish a journal Clinical Nutrition.

It was not the first society associated to clinical nutrition. ISPN, the International Society of Parenteral Nutrition, had been founded in 1966 to discuss the scientific work arising from the rapid development in Europe of parenteral nutrition in the late 50s and early 60s. ISPN, which counted both European and American members, held its meetings during the ICN Congresses in various parts of the world. The spreading interest in parenteral nutrition in the US in the 60s eventually led to the establishment of the American Society of Parenteral and Enteral Nutrition (ASPEN) in 1977.

ISPN had to redefine its role to better target the needs of those involved in clinical nutrition in Europe and it was decided that there was a need for an scientifically-orientated organisation providing a common ground for European scientists from many disciplines involved in nutritional support. A first informal meeting was therefore held in Stockholm in 1979 and invitations were sent to key individuals in the various European countries with an interest in clinical nutrition. Financial support was granted by a number of European industrial firms.

The following year a meeting of 800 participants was held in Newcastle where ESPEN was officially founded and its constitution agreed: the Society's officers would be a President, a Secretary, a Treasurer and two Auditors; there would also be a Council, consisting of one key member from each participating country who would elect members to the Executive Committee.

The success of the following meetings in terms of number of participants (Maastricht (1981) with 1300 participants, Vienna (1982) with 1800 participants) and industrial exhibitions showed that ESPEN was stimulating considerable interest both in the scientific and industrial world. Its growing responsibilities led to the establishment of a Scientific Committee that was to assist in giving scientific direction to the meetings and lay down guidelines to maintain high standards for abstract selection, evaluate and select abstracts and appoint reviewers for each topic; an Educational Committee, whose task it was to coordinate the educational aspects of the Society, and an Industrial Committee to develop links between ESPEN and industry.

The Society's rapid expansion in the following years called for further adjustments in terms of ESPEN's organisation and policy. A President in charge of organising the following congress would serve on the Executive Committee for one year, while a Committee Chairman would serve for four years to ensure continuity to ESPEN's policy. Research was promoted by offering a gradually increasing number of travel fellowships and ESPEN Research Fellowships. The first postgraduate course, run by the Educational Committee, was established in Brussels in 1984. Steps were taken to widen the participation of the members in running the affairs of the Society, and smaller additional meetings were held in Budapest and Tel Aviv to facilitate the spread of knowledge and provide scientific interchange in wider geographical areas. In time, the Scientific and Educational Committees were enlarged to include representatives of all discplines.

The Society's educational role has constantly been strengthened over the years: the congress educational programme, now expanded to two days, caters for specialist groups (nurses, dieticians, pharmacists, physicians) and the importance of postgraduate training is reflected in the increasing number of residential courses and workshops held throughout the years on specific topics. The Educational Committee was also made responsible for coordinating consensus statements on clinical nutrition, the results of which are published in Clinical Nutrition.

The years 1996 and 1997 marked yet another phase of growth of the Society. With a view to expanding its representativity and thus gaining some influence at the European policy-making level, ESPEN has offered National Societies involved in Clinical Nutrition the possibility of taking out block memberships for a reduced fee (Adapted from Clark, R. & Vinnars, E. "Early History of ESPEN" Clinical Nutrition 1994; 13:57-61). At the same time, ESPEN has launched the concept of the "Council Meeeting" which is organized at the occasion of the ESPEN Winter Meeting in January and at the occasion of the ESPEN congress in September. Each affiliated National PEN society has a representative who is invited to take part at these meetings. The objectives of the Council Meetings is to encourage interactivity amongst the diferrent PEN societies and Central ESPEN.

In 2005, ESPEN launched the Life Long Learning (LLL) program in Clinical Nutrition and Metabolism which is an innovative and effective educational program for medical doctors and health specialists offering training online and at live courses. At the occasion of the ESPEN congress (Brussels, 2005), 4 modules were presented for the first time. Each module consists of an updated review on a certain problem, clinical case, self-assessment test and grading quiz.  In 2018, this educational curriculum consists of 40 topics and 120 modules. To get the ESPEN diploma, participants have to accumulate credits and to pass final examination. For now, LLL courses are organized in countries around the world. More than 40'000 persons did follow modules.

In 2013, ESPEN organized the first "ESPEN Workshop" in Dubrovnik on the amino acids metabolism. This 2-days courses are designed by the ESPEN Scientific Committee and an LLL Course is organized immediately before the Workshop itseof. The Workshops were dedicated to "Lipid in ICU" (Tel Aviv, 2014), "Carbohydrates and Insulin Resistance" (Venice, 2015), "Nutrition in Cancer Patients" (Berlin, 2016), "Intestinal Failure" (Bologna, 2017) and "Nutrition in Peri-Operative Surgery" (Nottingham, 2018). In 2018, it has been decided to rename this so-called "Workshop" as a "Symposium".

The reputation of the journal "Clinical Nutrition" progressively increased for reaching an Impact Factor above 5.0 in 2018. The Editorial Board of Clinical Nutrition also decided to create an electronic on-line journal "Clinical Nutrition ESPEN" in 2011 which has been accepted to PubMed in 2017. Another journal "Clinical Nutrition Experimental" tghat has been created in 2015 is an open-access official journal of ESPEN. This journal (CNX) is intended to promote mainly basic science in the field of Clinical Nutrition.

The ESPEN congresses are annually organized early September in a different location in Europe. Since 2005, the congress also includes LLL modules and mixes scientific and educational sessions. Since 2015, the ESPEN congress is attracting more than 3'000 attendees, not only from Europe but from more than 60 different countries around the world. The number of abstratcts submissions is also steadily increasing for reaching more than 1'000 submissions in 2018. In September 2018, ESPEN celebrates its 40th Congress.

Following the publication of ESPEN Guidelines in the domain of enteral (2005) and parenteral (2009), the ESPEN Executive Committee in collaboration with the ESPEN Educational Committee decided in 2013 to publish disease-related Guidelines. Since this time, different Guidelines were released on Nutrition in Dementia (2015), Chronic Intestinal Failure (2016), Cystic Fibrosis (2016), Cancer Patients (2017), Polymorbid Internal Medicine Patients (2017) and Neurology (2017). Other Guidelines are under preparation. An updating process has been designed by the ESPEN Guidelines Committee.

Since 2007, ESPEN is an active stakeholder of the European Nutrition for Health Alliance (ENHA) that is a charity organization established to promote and to implement nutritional risk screening and improve nutritional care for all European citizens. ENHA members and partners are key European professional societies, associations and patients groups in public health and healthcare. ENHA works with the European Parliament for achiving its objectives. In 2014, ENHA designed the "Optimal Nutrition Care for All" campaign. In this campaign, ENHA supports European countries to establish/strengthen national multistakeholders platforms to implement nutritional screening and improve nutritional care. The country delegations meet twice a year to update the state of play, exchange good clinical practices and work on innovative projects.

In 2017, ESPEN has been officially accepted as an affiliated member society of UEG (United European Gastroenterology).

Amongst the educational activities, ESPEN is supporting the publication of the so-called "Blue Book" that contains basic knowledge in medical nutrition. The 5th edition of the Blue Book will be released early in 2019.