Following the disastrous floods of 1966 in Venice and Florence and the Italian Government's invitation one year later for UNESCO to play an international action, the Liaison Office for the Safeguarding of Venice was established in 1973 on the occasion of the UNESCO International Campaign for the Safeguarding of Venice. UNESCO Scientific Co-operation Bureau for Europe (SC/BSE) was established in 1972 as a separate unit attached to the office of the Assistant Director General for Sciences of UNESCO's Secretariat in Paris. In 1988, following the proposal of the Italian Government to host and support the activities of the Bureau for Scientific Co-operation, the Bureau was relocated to Venice, Italy and renamed as Regional Office for Science & Technology for Europe(ROSTE). Thanks to the substantial financial and logistical support provided by the Italian National Research Council (CNR) on behalf of the Italian Government, UNESCO ROSTE started its activities in 1989. Ten years later, within the frame of UNESCO's field strategy set out in the Decentralization Action Plan, UNESCO Bureau in Venice was renamed Regional Bureau for Science in Europe while maintaining its acronym ROSTE. In 2002, UNESCO established a single office in Palazzo Zorzi with the mandate to achieve UNESCO’s and Member States’ goals in the fields of science and culture.

In order better to reflect the scope of action of the UNESCO Office in Venice and after consultation with the Italian Government, UNESCO Director General on 27 March 2006 decided that this Office will henceforth be named the “UNESCO Office in Venice - UNESCO Regional Bureau for Science and Culture in Europe” (BRESCE). Engelbert Ruoss (Switzerland) serves as Director of the UNESCO Office in Venice since November 2006.