The position was created by Congress as a result of recommendations of the special commission investigating the terror attacks of Sept. 11, 2001.
"I commend the Senate for moving quickly to confirm John Negroponte as the first Director of National Intelligence," Bush said in a statement issued by the White House. "I congratulate John on his confirmation, and I look forward to working closely with him.
"As the DNI, Ambassador Negroponte will lead a unified intelligence community as it reforms and adapts to the new challenges of the 21st century."
Negroponte, former ambassador to Iraq and former U.N. ambassador, will oversee the 15 government agencies involved in intelligence collection and analysis.
He was approved 98-2 by the Senate.
White House Chief of Staff Andrew Card issued the oath of office less than an hour after the confirmation, with Bush looking on.