- James "Whitey" Bulger, brother of William M. Bulger and alleged organized crime head. Was on the FBI's Ten Most Wanted list until his arrest in Santa Monica, California on June 22, 2011. The film The Departed is partially based on his story as well as South Boston's criminal underworld.
- William M. Bulger, former president of the Massachusetts Senate, former president of the University of Massachusetts and brother of James "Whitey" Bulger.
- James Connolly, athlete and author who, in 1896, became the first modern Olympic champion.
- John Cunniff, National Hockey League hockey coach and former professional player who appeared in 65 World Hockey Association regular season games between 1972 and 1976.
- Richard Cushing, prelate of the Roman Catholic Church who served as Archbishop of Boston from 1944 to 1970, and was elevated to the cardinalate in 1958.
- John Ferruggio, led the evacuation of Pan Am Flight 93 in 1970
- Michael F. Flaherty, an at-large member of Boston City Council. He is a member of the Democratic Party and was elected City Council President every year from 2002 to 2006.
- Raymond Flynn, Mayor of Boston from 1984 to 1993, and United States ambassador to the Holy See from 1993 to 1997.
- Brian Goodman, film and television director, writer, and actor.
- David Lindsay-Abaire, Pulitzer Prize-winning playwright and lyricist.
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- Edward Lawrence Logan, National Guard General, politician, and namesake of Logan International Airport
- Barbara Lynch, Chef and owner of the Barbara Lynch Gruppo restaurant group.
- Stephen Lynch, politician, a Democratic member of the United States House of Representatives. He was one of the lead investigators in the "Banned substances in baseball" investigation.
- Michael Patrick MacDonald, activist against crime and violence and author.
- John William McCormack, politician who served as a member of House of Representatives from 1928 until he retired from political life in 1971. A member of the Democratic Party, he served as House Majority Leader three times, and as Speaker of the House of Representatives from 1962 until 1971.
- Will McDonough, sportswriter for The Boston Globe and television analyst.
- Joe Moakley, Democratic Congressman, and the last chairman of the United States House Committee on Rules.
- Patrick Nee, former mobster, Vietnam veteran, author. Former associate of James "Whitey" Bulger.
- Brian Noonan, Hockey player who won the Stanley Cup in 1994 with New York Rangers.
- Kevin Weeks, former mobster, and former lieutenant to James Bulger in the Winter Hill Gang, Federal witness, and author.
- James M. "Jim" Kelly, Former Boston City Councilor, Council President and community activist.
- James Healy America's first Catholic bishop of African descent.
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