He was first elected leader of the conservative Union Nationale party in 1961. The party had governed Quebec with Maurice Duplessis as its leader from 1935 until its defeat in 1960 by the Quebec Liberal Party of Jean Lesage. The UN's defeat is seen as the beginning of the Quiet Revolution, which sought to overturn the domination of the Quebec economy by English-speking people, and the dominant role of the Catholic Church in Quebec Society.
In 1965, his book entitled, Égalité ou indépendance (Equality or independence), made him the first leader of a Quebec political party to recognise the possibility of independence for Quebec. His position on the issue was ambiguous: as he wrote in his book, his position was for "independence if necessary, but not necessarily independence".
Under the same slogan, Égalité ou indépendance, he was elected as premier of Quebec in 1966. He retained this position until his death in 1968. His term was, among other things, qualified by tensions with the Government of Canada over constitutional matters.