Schlesinger was 85. His daughter said he was hospitalized at the Johns Hopkins Bayview Medical Center.
An economist with a Harvard doctorate, Schlesinger taught at the University of Virginia and worked for the RAND Corp. before going to work as a budget adviser to President Richard Nixon in 1969. During the next decade, he headed the Atomic Energy Commission, the CIA and the departments of Defense and Energy.
Nixon named Schlesinger secretary of defense in 1973 as the United States with winding down its involvement in Vietnam. During the next two years, he battled Congress over the defense budget and took a hard line against the Soviet Union.
Schlesinger later confirmed that in August 1974 in the last days of the Nixon administration he warned military leaders to clear any orders from the White House with him or Secretary of State Henry Kissinger.
Schlesinger clashed with President Gerald Ford, who was willing to compromise with Congress on defense spending and supported amnesty for the young men who dodged the Vietnam-era draft. Ford fired him in November 1975.
President Jimmy Carter named Schlesinger to head the newly created Department of Energy, the only Republican in his cabinet. Schlesinger lost his job in a 1979 shakeup.
In his later years, Schlesinger headed investigations into the abuse of prisoners at Abu Ghraib Prison in Iraq and the treatment of detainees at Guantanamo Bay.