Sherman was born into a Jewish family in Toronto to Herbert Dick "Hyman" Sherman (1906–1952), a Business partner for a zipper company, and Sara "Sarah" Sherman (née Winter; 1910–1971), an occupational therapist after her husband's death. His grandparents from both sides had fled persecution of Jews in Russia and Poland. His Father died from heart attack when Bernard was still young at the age of 10. He won a national physics contest while attending the Forest Hill Collegiate Institute and graduated with top marks. He entered the University of Toronto's engineering science program at age 16, believed to be the youngest to do so. The same year, he signed up for a Canadian Army organized student militia. He graduated with the highest honours in his class and received the university's Governor General's Award for his thesis. In 1967, he completed a PhD in astrophysics from Massachusetts Institute of Technology.

Sherman married Honey Reich (1948–2017), in 1971, a fellow University of Toronto graduate born in 1948 (sic) in Austria to Polish Holocaust survivors. They had four children, a son, Jonathon, and three daughters, Lauren, Alexandra and Kaelen.

In 1967, after completing his PhD, Sherman purchased the Empire Group of Companies from the executor of the estate of his aunt and uncle, Beverley and Louis Lloyd Winter, as both had died seventeen days apart in November 1965, leaving four orphaned young children: Paul Timothy, Jeffrey Andrew, Kerry Joel Dexter, and Dana Charles. Prior to the purchase, Empire was the first to secure the compulsory rights to manufacture Hoffmann-La Roche's Valium (diazepam), and was one of Canada's largest manufacturers of Pfizer's Vibramycin (doxycycline), Upjohn Company's Orinase (tolbutamide), and the dietary sweetener saccharin. To facilitate the corporate acquisition, Sherman along with his high school friend, Joel Ulster (Sherman and Ulster Limited), offered 5% equity options to each of the four children and a 15-year royalty on four of its patented products.

In 1970 he invested in New York's Barr Laboratories with US-based partners, became its largest shareholder and served as Barr's President. As of 2000, he controlled about 33% of Barr Laboratories' stock. Barr won the first rights to manufacture generic versions of Eli Lilly's Prozac. Today, Barr Laboratories' is a part of Teva Pharmaceutical Industries, the world's largest generic drug maker, following Teva's acquisition of Barr Pharmaceuticals in 2008.

In January 1972, Sherman and Ulster Limited sold Empire Laboratories to the Quebec-based Canadian operations of publicly traded International Chemical and Nuclear (ICN) of California, for 57,000 shares (Valeant Pharmaceuticals). In 1973, Sherman started Apotex with a few former Empire Laboratories' personnel and he incorporated it in 1974. This privately owned and Sherman-controlled company claims to be Canada's largest Canadian-owned pharmaceutical manufacturer. Sherman also became involved in Nutraceutical Manufacturing and other businesses, founding NION (National Institute of Nutrition) with Richard Kashenberg. He later sold the company to Schiff and continued on to Apotex.

Sherman, with his wife, donated a record $50 million to the United Jewish Appeal. They provided funds to build a major addition to the geriatric Baycrest centre, and to other Toronto-area community centres in Ontario. The couple were also major donors to the United Way. As well, the Apotex Foundation had sent over $50 million worth of Medicine to disaster zones since 2007.

In 2011, the Winter children (his cousins) sued Sherman alleging he never paid royalties and equity in Apotex, contending Sherman had used the proceeds from the 1972 sale of their late father's Business Empire to buy Apotex in 1973. The cousins sought a 20% interest in Apotex or damages of $1 billion. Sherman responded by withdrawing millions of dollars in financial assistance to his cousins. The cousins' contended that Sherman "had offered the financial assistance in the first place in order to make the cousins dependent on him, and to keep them from learning about their rights to the business", though this was denied by Sherman. In September 2017, an Ontario Superior Court justice ruled against the cousins, saying the case was "wishful thinking, and beyond fanciful." At the time of the judgement, a Lawyer for the cousins said they would appeal, though no appeal occurred, and Sherman died a few months later under unknown circumstances.

At the time of his death, Sherman was under investigation because of a fundraiser he had held for Justin Trudeau in April 2015, allegedly contrary to Canada's lobbying rules. Sherman filed a lawsuit in May 2016, attempting to quash the investigation. "There is basis to conclude that Mr. Sherman is in breach of ... the Lobbyists’ Code of Conduct as a consequence of his involvement in the organization of a fundraising event for the (Liberal Party)," according to Phil McIntosh, Director of investigations at the Office of the Lobby Commissioner. If that had been proven, Sherman would have been banned from lobbying for five years.

By 2016, Apotex employed over 10,000 people as one of Canada's largest drug manufacturers, with over 260 products selling in over 115 countries. Revenues were about $1.5 billion annually.

Toronto Police Service had previously told the news media that there was no indication of forced entry into the Sherman home and that their investigation does not include a search for any suspects. Although there was no note left by the deceased, police sources told the Toronto Star on December 15 or 16, 2017, that they were "probing the possibility that they were a murder–suicide". In response, the couple's four children issued a statement urging the police to conduct a thorough Criminal investigation and chastised the police for leaking a murder-suicide theory. They also contacted Toronto Lawyer Brian Greenspan to retain a private investigator to look into the deaths. He hired Tom Klett, a retired Toronto Police detective who has worked in the homicide, drug, and intelligence bureaus. The family also hired Dr. David Chiasson, the retired chief forensic pathologist for Ontario, to conduct another autopsy.

On January 20, 2018, the Toronto Star published an exclusive report based on anonymous sources from the family's investigation team who said that the cause of death was murder: the couple was strangled by belts after their hands were tied. These investigators had not yet gained access to the Sherman home. "People providing information for this story are not identified as they were not authorized to discuss the case," according to the Star. When contacted by a reporter, a Toronto Police spokesman reiterated the position that they were treating the deaths as "suspicious". On January 26, Toronto Police advised the news media that their investigation concluded that the couple had been murdered in a targeted attack. At the time, they would not discuss any possible suspects, but planned to interview everyone who had access to the home prior to the deaths via the lockbox that was previously installed by the real estate agent. The police investigation has encountered resistance at Apotex headquarters, with a police spokesman saying “Legal complexities in some executions have been challenging given the litigious nature of Barry Sherman’s businesses, in particular the search and seizure of electronics in Barry Sherman’s workspace at Apotex”.

A partial draft of his unpublished memoir, called Legacy of Thoughts, was submitted as part of Sherman’s motion for summary judgment in a lawsuit brought by his orphaned cousins. He described the manuscript as his observations on philosophy, Canadian politics and the pharmaceutical industry. Sherman did not believe in God, free will, altruism or morality. "I find no inconsistency in holding intellectually that life has no meaning, while at the same time being highly motivated to survive and to achieve", he once said.