He served as a member of the Massachusetts state house of representatives from 1977 to 1985. He then became a member of the Massachusetts state senate, serving from 1985 to 1991. From 1991 to 1997 he was Lieutenant Governor of Massachusetts, becoming the Republican governor of Massachusetts in 1997. In 2001 he became Ambassador to Canada.
In April 2003 Cellucci caused an uproar in Canada when he criticized the country for perceived lack of support for the U.S.-led invasion on Iraq. Cellucci's daughter Anne is married to a Canadian hockey player, Craig Adams.