Raines earned a bachelor's degree from Birmingham-Southern College in 1964 and later a master's in English from The University of Alabama. The University of Alabama also awarded him an honorary doctorate in 1993. In 1964, Raines began his newspaper career as a reporter for the Tuscaloosa News in Alabama. He also reported for WBRC-TV in Birmingham. After a year as a reporter at the Birmingham News, Raines became political editor of the Atlanta Constitution in 1971. His position at the newspaper lasted until 1976, when he became political editor at the St. Petersburg Times.

Raines' affiliation with The New York Times began in 1978, when he joined as a national correspondent based in Atlanta. By 1979, Raines was the bureau chief in Atlanta, a position he remained in until 1981, when he became a national political correspondent. By the next year, Raines had been promoted to a White House correspondent for The Times. His ascent within management continued in 1985, when he became deputy Washington editor. In 1987, Raines transferred to London and worked as the newspaper's London bureau chief. The next year, he returned to Washington D.C. to become the Washington bureau chief. In 1992, he was awarded the Pulitzer Prize for Feature Writing. His longest lasting assignment within The Times began in 1993, when he left Washington for New York to become the paper's editorial page editor. He was appointed to Executive Editor in September 2001.Paul Krugman, a Times columnist, stated in his book, The Great Unraveling, that it was Raines who made the decision to hire him.

Raines was lauded by many for instituting a program to increase diversity and to revive advocacy journalism. Although there was a period in the early unfolding of the Enron story regarding that energy company's corrupt practices when the Times had to play 'catch up' to the Wall Street Journal, the Times did later develop some hard-hitting articles on that subject, a highly praised accomplishment due in part to Raines' insistence on aggressive investigations.

Following the Jayson Blair scandal, Raines resigned his position at the Times.

Raines took a look at his tenure as Executive Editor in "My Times", published in the Atlantic Monthly, and again in his memoir The One that Got Away, which came out in 2006. In it, Raines juxtaposes fishing stories with his journalism career, with particular attention to what led up to the Jayson Blair scandal.

Raines appeared as a guest on the television show The Colbert Report on July 24, 2006. He and Colbert's discussion touched on subjects including the release of his new book and the Jayson Blair scandal.

On January 14, 2008, it was announced that Raines will become a media columnist for Condé Nast Portfolio. His first column was published in the March issue of the magazine, and analyzed the possibilities of Rupert Murdoch buying, and therewith, from Raines' point of view, damaging The New York Times.

Raines penned an op-ed in the March 14, 2010 edition of The Washington Post that was highly critical of Fox News Channel and the fact that journalists leave Fox's journalism largely unchecked, without mentioning his role in the Jayson Blair incident.

In addition to his work as a journalist, Raines has published several books; My Soul Is Rested and Whiskey Man in 1977 and Fly Fishing Through the Midlife Crisis in 1993. He contributed to Campaign Money, published in 1976.