He took over the position in the wake of the debacle of Mutiny on the Bounty (1962). Under O'Brien's regime, in partnership with head of producer Robert M. Weitman, MGM produced its last run of classic films, including Dr Zhivago (1965), The Dirty Dozen (1967) and 2001: A Space Odyssey (1968). A series of flop films such as The Shoes of the Fisherman and Ice Station Zebra saw him removed from his position as president in 1969.
He was replaced by Louis F. Polk Jr. and was instead appointed chairman. In May 1969 as MGM was headed towards a $6 million loss for the first half of the year, O'Brien resigned as chairman and was replaced by Edgar Bronfman, Sr., the largest shareholder of MGM.