He was the grand-nephew of Andrew Mellon, a banker and secretary of the Treasury who was involved with some of the biggest industrial companies of the early 20th century. Forbes magazine estimated Scaife's net worth in 2013 at $1.4 billion.
The intensely private Scaife became widely known in the 1990s when first lady Hillary Rodham Clinton said her husband was being attacked by a "vast right-wing conspiracy." White House staffers and other supporters suggested Scaife was playing a central role in the attack.
Several foundations controlled by Scaife gave millions of dollars to organizations run by critics of Clinton, including $1.7 million for a project at the conservative American Spectator magazine to dig up information about his role in the Whitewater real estate scandal.
Scaife rarely gave interviews, but in a sit-down with George magazine editor John F. Kennedy Jr. in 1998, he called President Clinton "an embarrassment."
In the interview, Scaife denied that his money helped support an effort to hurt the president, but he suggested Clinton might be linked to the deaths of dozens of administration officials and associates, including White House Deputy Counsel Vince Foster and onetime Commerce Secretary Ron Brown. Foster's death was determined to be a suicide; Brown died in a plane crash.
Scaife also accused Kenneth Starr, the independent counsel whose investigation led to Clinton's impeachment in the Monica Lewinsky sex scandal, to be a "mole working for the Democrats."
Scaife's stance toward the Clintons softened years later. In an interview published in early 2008, he told Vanity Fair magazine he and the former president had a "very pleasant" lunch the previous summer, and "I never met such a charismatic man in my whole life."
Clinton gave Scaife an autographed copy of his book, and Scaife said he later sent $100,000 to the Clinton Global Initiative. (Scaife also said philandering "is something that Bill Clinton and I have in common.")
Scaife's newspaper also endorsed Hillary Rodham Clinton's bid for president in 2008.
Despite funding many causes dear to conservatives, Scaife was libertarian on many social issues. He supported Planned Parenthood and abortion rights, supported legalizing same-sex marriage and marijuana, and opposed the invasion of Iraq in 2003.
Scaife bought the Tribune-Review in suburban Pittsburgh in 1969, using its editorial pages to trumpet his views.
"I fell in love with newspapers as a boy, when my father bought me editions from around the country and abroad," Scaife told readers in the column announcing his cancer diagnosis. "The day I became a newspaper publisher, buying the Tribune-Review, remains one of the proudest, happiest moments of my life."
Pennsylvania Gov. Tom Corbett said in a statement Friday that Scaife's passing "marks the departure of a man whose vision and generosity shaped the city's progress and our nation's course." He said his contributions helped to preserve Pittsburgh's landmarks.
Corbett also cited Scaife's investment in think tanks that he said "reshaped our nation's political dialogue and delivered the opening salvos in the Reagan revolution, replacing tired nostrums with vigorous new ideas for progress."
Scaife was a longtime supporter of Republicans, backing presidential candidate Barry Goldwater in 1964 and heavily funding the 1968 campaign of Richard Nixon.