Brock was born in Washington, D.C., and adopted by Dorothea and Raymond Brock. He has a younger sister, Regina. Brock's family was Catholic and his father held strong conservative beliefs.

Brock graduated from Paramus High School in Paramus, New Jersey and then attended the University of California, Berkeley. There he worked as a reporter and editor for The Daily Californian, the campus newspaper, sometimes expressing conservative views. He was an intern at The Wall Street Journal. He graduated from Berkeley with a B.A. in History in 1985.

In 1986, he joined the staff of the weekly conservative news magazine Insight on the News, a sister publication of The Washington Times. After a stint as a research fellow at the Heritage Foundation, in March 1992 Brock authored a sharply critical story about Clarence Thomas' accuser, Anita Hill, in The American Spectator magazine. A little over a year later, in April 1993, Brock published a book titled The Real Anita Hill which expanded upon previous assertions that had cast doubt on the veracity of Anita Hill's claims of sexual harassment.

The book became a best-seller. It was later attacked in a book review in The New Yorker by Jane Mayer, a reporter for The New Yorker, and Jill Abramson, a reporter for The Wall Street Journal. The two later expanded their article into the book Strange Justice, which cast Anita Hill in a much more sympathetic light. It, too, was a best-seller. Brock replied to their book with a book review of his own in The American Spectator.

In the January 1994, issue of The American Spectator, Brock, by then on staff at the magazine, published a story about Bill Clinton's time as governor of Arkansas that made accusations that bred Troopergate. Among other things, the story contained the first printed reference to Paula Jones, referring to a woman named "Paula" who state troopers said offered to be Clinton's partner. Jones called Brock's account of her encounter with Clinton "totally wrong," and she later sued Clinton for sexual harassment, a case which became entangled in the Independent Counsel's investigation of the Whitewater scandal and eventually led to the impeachment of the president. The story received an award later that year from the Western Journalism Center, and was partially responsible for a rise in the 25-year-old magazine's circulation, from around 70,000 to over 300,000 in a very short period.

Three years later, Brock surprised conservatives by publishing a somewhat sympathetic biography of Hillary Clinton, titled The Seduction of Hillary Rodham. Having received a $1 million advance and a tight one-year deadline from Simon & Schuster's then-conservative-focused Free Press subsidiary, Brock was under tremendous pressure to produce another best-seller. However, the book contained no major scoops. In Blinded by the Right (2002), Brock said that he had reached a turning point — he had thoroughly examined charges against the Clintons, could not find any evidence of wrongdoing, and did not want to make any more misleading claims. Brock further said that his former friends in right-wing politics shunned him because Seduction did not adequately attack the Clintons. He also argued that his "friends" had not really been friends at all, due to the open secret that Brock was gay.

In July 1997, Brock published a confessional piece in Esquire magazine titled "Confessions of a Right-Wing Hit Man", in which he recanted much of what he said in his two best-known American Spectator articles and criticized his own reporting methods. Discouraged at the reaction his Hillary Clinton biography received, he said, "I... want out. David Brock the Road Warrior of the Right is dead." Four months later, The American Spectator declined to renew his employment contract, under which he was being paid over $300,000 per year.

Writing again for Esquire in April 1998, Brock apologized to Clinton for his contributions to Troopergate, calling it simply part of an anti-Clinton crusade. He told a more detailed story of his time inside the right wing in his 2001 memoir, Blinded by the Right: The Conscience of an Ex-Conservative, in which he settled old scores and provided inside details about the Arkansas Project's efforts to bring down Clinton. Later, he also apologized to Anita Hill.

In 2001, Brock accused one of his former sources, Terry Wooten, of leaking FBI files for use in his book about Anita Hill. Brock defended his betrayal of a confidential source by saying, "I've concluded that what I was involved in wasn't journalism, it was a political operation, and I was part of it...So I don't think the normal rules of journalism would apply to what I was doing."

Brock directly addressed the right-wing "machine" in his 2004 book, The Republican Noise Machine, in which he detailed an alleged interconnected, concerted effort to raise the profile of conservative opinions in the press through false accusations of liberal media bias, dishonest and highly-partisan columnists, partisan news organizations and academic studies, and other methods. Also in 2004, he featured briefly in the BBC series The Power of Nightmares, where he stated that the Arkansas Project engaged in political terrorism.

About the same time he founded Media Matters for America, an Internet-based progressive media watchdog group "dedicated to comprehensively monitoring, analyzing, and correcting conservative misinformation in the U.S. media".