In 1965, the Accademia della Crusca launched the project of a new historical dictionary of Italian, funded by the the Italian National Research Council (CNR), and to that end it created an organization named Opera del Vocabolario Italiano, which was directed by Aldo Duro until 1972, by Giovanni Nencioni until 1974, and by d’Arco Silvio Avalle from 1974 onwards.

Through the Italian law no. 6, of 06/01/1983, the OVI staff was absorbed by the CNR. By virtue of the same law, and in agreement with the Accademia della Crusca, in 1985 the CNR Center for the Study of the Opera del Vocabolario Italiano was established with Carlo Alberto Mastrelli as director. Mastrelli served in that role until 1992 when he was succeeded by Pietro G. Beltrami.

As part of the internal reorganization of the CNR scientific network, in 2001 the OVI  became a CNR institute, within the Department of Social and Human Sciences - Cultural Heritage (DSU). The direction of Pietro G. Beltrami continued until September 2013, after which Paolo Squillacioti took over as acting director until September 2014. On October 1, 2014, Lino Leonardi became the new OVI director.

From October 1, 2014 to September 30, 2018, the OVI was directed by Lino Leonardi; at the end of the mandate, Paolo Squillacioti took over again as acting director.