General Hayden takes over the spy agency with a pledge to boost morale and make it more aggressive after it was caught flat-footed on the September 11, 2001 attacks and provided flawed intelligence about weapons of mass destruction in Iraq.
General Hayden was confirmed on a 78-15 vote, providing a broad bipartisan endorsement to the architect of President George W Bush's domestic spying program. He has been principal deputy to US intelligence chief John Negroponte up to now.
President Bush applauded the Senate's bipartisan vote and said of General Hayden: "Winning the war on terror requires that America have the best intelligence possible and his strong leadership will ensure that we do."
General Hayden replaces Porter Goss, who was forced to resign earlier this month after clashing with Mr Negroponte amid widespread concern about the future of the spy agency.
Twenty-six Democrats and the Senate's lone independent joined 51 Republicans voting for Hayden. Only one Republican, Pennsylvania's Arlen Specter, who chairs the Senate Judiciary Committee, voted against General Hayden and he said it was in protest over National Security Agency (NSA) actions.
General Hayden, an air force general, was NSA director when President Bush ordered the domestic eavesdropping program in the aftermath of the 9/11 attacks.
Critics say it exceeds the president's constitutional powers and violates a federal law requiring court warrants for eavesdropping inside the US.
Senator Specter said the Bush administration had not fully complied with a law on notifying Congress of the spying program, which allows for monitoring of international phone calls and emails of US citizens without warrants while pursuing al-Qaeda suspects.
Instead, a select group of the committee was briefed, with a full briefing only "in the few days prior to the confirmation hearings on General Hayden", the Senator said.
Besides Mr Specter, dissenting votes came from 14 Democrats who expressed concern over the NSA spying program.
Senator Edward Kennedy of Massachusetts was one of those Democrats. "Until there is a full accounting of the surveillance program, I cannot in good conscience support a promotion for its chief architect," Kennedy said.
But most Democrats appeared to take the lead of influential party members, including Senator John Rockefeller of West Virginia, vice chairman of the Senate Intelligence Committee, who has called Hayden an experienced and independent leader capable ofrestoring the CIA's credibility.