Lawmakers in the US Senate earlier on Thursday voted 98-2 to approve President George Bush's nominee, who in the coming months is expected to oversee sweeping changes in the American intelligence community.
As the new intelligence chief, Negroponte is charged with coordinating the activities of 15 spy agencies, including the CIA, and serving as Bush's top adviser on intelligence.
Bush attended the hastily arranged White House swearing-in ceremony for Negroponte.
White House spokesman Scott McClellan said Negroponte would soon take over CIA responsibility for giving the president his daily intelligence briefing.
His new position replaces the director of central intelligence, a title CIA Director Porter Goss had held since September. Goss replaced former CIA director George Tenet, who resigned last summer after presiding over the September 11 and Iraq intelligence lapses.
Republican and Democratic lawmakers alike said Negroponte's long experience with intelligence officers in Vietnam, Central America and Iraq made him knowledgeable about espionage but unburdened by the politics of the intelligence community.
But the senators predicted he would face a tremendous challenge trying to bring meaningful change to an intelligence community that has largely proved immune to reform.