At the 2002 Alpbach Technology Forum Anton Zeilinger suggested establishing a new outstanding institute for basic research. A draft concept was presented in 2005. The legal basis for the institute is the 2006 Federal Law on the Establishment of the Institute of Science and Technology Austria (IST Austria). An International Committee consisting of Haim Harari, Olaf Kübler, and Hubert Markl published a report which became the blueprint for the Institute in June 2006. The Board of Trustees was formed in December 2006.

Until the first president was appointed, all executive tasks of IST Austria were in the hands of the Executive Committee of the Board of Trustees, chaired by Haim Harari. In particular, until August 2009 Harari led the campus development and faculty hiring and set up all necessary organizational structure. The first employee, Gerald Murauer, was hired at the beginning of 2007, as an interim manager, and was later appointed by the first president as Managing Director. The staff grew slowly and reached half a dozen by the fall of 2007.

The search for the first president was launched in early 2008, with the Executive Committee of the Board of Trustees serving as search committee. Several dozen candidates were considered. The Board of Trustees finally elected Thomas Henzinger at the end of 2008. He participated in all major decisions, in particular, in the recruitment of new professors, throughout 2009 and started his full-time employment at the Institute in September 2009.

IST Austria was inaugurated in June 2009, when the first theoretical research groups moved into the central building and the administration moved into the voestalpine administration building. In addition, the lecture hall, guest house, campus restaurant and utility infrastructure started operating in 2009. The first laboratory building, the Bertalanffy Foundation Building, was opened for experimental research groups in October 2010, Lab Building East in November 2012, and Lab Building West in December 2015. More than 40 research groups are working on campus. The planned campus development will allow a growth of up to 90 research group by 2026.

Bertalanffy Foundation Building under construction