Dreyfus died at New York Presbyterian Weill-Cornell Medical Center, a hospital spokeswoman said.
The cause of his death wasn't immediately known, but he had been ill for some time, said Arnold Friedman, treasurer of the Dreyfus Charitable Foundation, the financier's philanthropy.
As the creator of the Dreyfus Fund and its parent Dreyfus Corp., Dreyfus built one of the first mutual fund firms to actively court everyday individuals rather than just professional financiers and institutions.
The fund's lion symbol -- introduced in a cheeky ad that showed the big cat striding out of a subway station and down Wall Street -- became a familiar mark of success and power to generations of Americans.
During the 12 years he ran the Dreyfus Fund, it returned 604% -- more than 100 percentage points better than its closest competitor, according to a 2004 Investor's Business Daily article that described his method of charting stocks on giant sheets of graph paper.
Life magazine called him a "maverick wizard." He dubbed himself "the lion of Wall Street" in a 1996 book, one of at least five he wrote.
Dreyfus kept following the market and going to an office overlooking Central Park every day into his 90s, though he retired from the Dreyfus Corp., which is now a part of the Bank of New York Mellon Corp., in 1965. He left with an estimated net worth of $100 million and a new mission.
He also was a high-ranking bridge and gin rummy player, bred champion race horses and won tennis tournaments for players in their 60s and 70s, his foundation said.
Behind the scenes, he had been fighting severe depression -- cured, he said, only when a doctor prescribed the anti-epilepsy drug Dilantin.
Dreyfus threw himself into promoting the use of the drug to treat depression. He spent more than $2 million on ads, pressed Presidents Nixon and Reagan and described his struggle in books including "A Remarkable Medicine Has Been Overlooked."
The Food and Drug Administration has never approved the drug to treat depression, but Dreyfus' campaign entangled him in political controversies.
A 2000 book by journalist Anthony Summers about Nixon, "The Arrogance of Power," said Dreyfus gave Dilantin to the president. Dreyfus told the New York Times the claim was true, but some Nixon aides and Patricia Nixon Cox, the former president's daughter, called it doubtful.
The next year, it was revealed that Dreyfus had given Oklahoma Gov. Frank Keating $250,000 during the 1990s and Keating had arranged for Dreyfus to talk with state and federal officials about the drug. Keating said he had done nothing wrong, but returned the money.
Born Aug. 28, 1913, in Montgomery, Ala., Dreyfus said he wasn't much of a student growing up or at Lehigh University.
He started a brokerage house in 1947 before launching his mutual fund in 1951, the Dreyfus Corp. said.
Information on survivors was not immediately available.