The Senate had earlier approved Mr Negroponte’s nomination by a majority of 98-2.
The new spy chief will take primary responsibility for delivering the president’s daily intelligence briefing and will set budgets for the intelligence agencies.
In a 40-year diplomatic career, Mr Negroponte has served as American ambassador to Iraq and to the United Nations.
After being nominated for the new post, he faced tough questioning from the Senate Intelligence Committee about his time as ambassador to Honduras, where human rights groups allege that he acquiesced in abuses by death squads.
What are your fondest memories of the Reagan administration?