Weiss grew up in New York City and attended public schools, including the Bronx High School of Science. He received degrees from the City College of New York and the Medill School of Journalism at Northwestern University. He worked for news organizations in Connecticut and Washington, D.C., and Barron's magazine, before joining Business Week magazine in 1986.

Between 1986 and 2004 Weiss wrote investigative articles for Business Week, including cover stories on the dangers of the Internet, as well as stock fraud and improprieties by brokerages large and small. His articles described widespread improper trading at the American Stock Exchange and broke the story of the bond trading scandal at Salomon Brothers in 1991. Weiss also wrote essays and articles critical of the Securities and Exchange Commission and other regulators., and a 1995 cover story exploring the early manifestations of online investing.

In testimony before a U.S. Senate committee in 1991, Warren Buffett, then temporarily running Salomon Brothers, said that he learned of a bond trading scandal by reading Weiss' article in Business Week. At the time the article came out, he said, Salomon Brothers was denying a scandal was taking place. Buffett said, "I was not that aware personally about the squeeze, not until I did read that Business Week story."

Weiss authored a cover story in the April 1, 1996 edition, titled "Fall of the Wizard," that was critical of Julian Robertson's performance and behavior as manager of hedge fund Tiger Management. In response, Robertson sued Weiss and BusinessWeek for $1 billion for defamation. The suit was settled with no money changing hands, and BusinessWeek standing by the substance of its reporting. After two years of poor performance, the Tiger funds closed in 2000.

Weiss' cover story "The Mob on Wall Street", published in December 1996, described how New York's organized crime families had infiltrated brokerage firms in New York and Florida. The article named the firms and crime figures involved, and described how they defrauded thousands of investors around the country. This story preceded the June 2000 arrest of 120 Mafia figures for stock fraud by almost four years.

In 1998, Weiss wrote a Business Week commentary calling for strict limits on leverage, saying "limiting leverage may make some high-tech investment strategies difficult or impossible. It might also cut into the derivatives business of banks and Wall Street firms. If that's the case--well, so be it."

Weiss's "Mob on Wall Street" and other Business Week stories were praised by then-FBI Director Louis Freeh, in a letter published by Business Week in December 2000. Freeh wrote: "Gary Weiss has done our nation an invaluable service by reporting the manipulation of the stock market by elements of organized crime. By outlining specific stocks and stock brokerage firms that were controlled by organized crime, he opened the door for FBI investigations in Florida and in New York, and for that we owe him a tremendous debt of gratitude."

Born to Steal, published in 2003, reports on a Mafia-linked stockbroker named Louis Pasciuto. The book describes how Wall Street firms were infiltrated by organized crime figures during the 1990s.

Wall Street Versus America, published in April 2006, is described as an "attack, using humor and ridicule" on the morality of Wall Street, its regulators and the financial press. The book is critical of hedge funds, mutual funds, and the Wall Street securities arbitration process, as well as the New York Stock Exchange. The book is also critical of former Securities and Exchange Commission chairmen Arthur Levitt and William H. Donaldson. The book is strongly critical of the campaign against naked short selling, because Weiss believes it threatens the ability of short sellers to deflate pump-and-dump schemes, thus providing cover to the scam artists behind such schemes.