Bronfman held various positions in the family's liquor empire, Seagrams, from 1951 to 2000. In 1951 Bronfman's Father Samuel Bronfman gave Charles a 33% ownership stake in Cemp Investments, a holding company for him and his 3 siblings which controlled the family's corporate empire. Under the leadership of Charles and brother Edgar, it controlled billions of dollars in liquor, real estate, oil and gas, and chemical companies.

Bronfman was also well known for his forays into professional Sports. He was majority owner of the Montreal Expos franchise in Major League Baseball from the team's formation in 1968 until 1990. In 1982, a day after the Montreal Alouettes of the Canadian Football League collapsed due to financial troubles, Bronfman bought their remains and used them to start a new franchise, the Montreal Concordes. This venture proved far less successful – despite later rebranding the team as the Alouettes, the team folded prior to the start of the 1987 CFL season.

Bronfman and his brother, Edgar, inherited the Seagram spirits empire in 1971 after the death of their Father, Sam Bronfman. Bronfman is a former Co-Chairman of the Seagram Company Ltd. On the demise of the company: "It was a disaster, it is a disaster, it will be a disaster," he says. "It was a family tragedy."

Since 1986, he has served as Chairman of The Andrea and Charles Bronfman Philanthropies, Inc. He plans to close the foundation in 2016.

From November 1997 until July 2002, Bronfman was the Chairman of the Board of Koor Industries Ltd., one of Israel's largest investment holding companies. He is the co-chairman of the McGill Institute for the Study of Canada. From 1999 to 2001, Bronfman was the first Chairman of the United Jewish Communities, the merged North American organization comprising United Jewish Appeal, the Council of Jewish Federations and United Israel Appeal.

He and Michael Steinhardt co-founded Taglit Birthright, a program which provides a free, educational travel experience to Israel for young Jewish adults. Bronfman is one of its principal donors. Since 1999, the program has sent more than 340,000 young Jews from around the world on a 10-day free trip to Israel.

In April 2013, Bronfman was one of 100 prominent American Jews who sent a letter to Israeli Prime Minister Benjamin Netanyahu urging him to "work closely" with Secretary of State John Kerry "to devise pragmatic initiatives, consistent with Israel's security needs, which would represent Israel's readiness to make painful territorial sacrifices for the sake of peace."

Bronfman was a founding co-chairman of Historica, producers of the Heritage Minutes series of television shorts. It was at an early meeting of this foundation (originally the CAB Foundation) that he asked the members, "If television can use 30 seconds or 60 seconds to persuade people that Cadillacs or cornflakes are interesting, couldn't we also use that short piece of time to persuade Canadians that their history is interesting? You tell me how to do it, and I'll fund it." It was out of that discussion that the Heritage Minutes were conceived, piloted, distributed through cinemas and broadcasters across the country, and then confirmed as a major contribution of the Foundation — which a few years later became Historica, recently merged with the Dominion Institute.