Arriving at CERN as a leader of a French experimental team, he was appointed Directorate member for research in 1964. Director-General from January 1966 until December 1970, he preceded John Adams and Willibald Jentschke.

Two major events took place during Bernard Gregory's years as Director-General. Prior to his term of office the decision to build the ISR machine had been taken by Council in 1965. Construction began immediately and was completed by the end of 1970. The second major event was the decision to build a 300 GeV Proton Synchrotron. A proposal had been put to Council in 1964 whilst Victor F. Weisskopf was Director-General of CERN but it was not until the end of Bernard Grego ry's term of office that Council agreed to the project.

From 1971-1973 he served as Chairman of the ISR Committee, and was a Council Delegate for France from 1971, and Vice-President from 1974. He had been elected as Chairman of Council, when he died unexpectedly in December 1977.