Syed Rizwan Farook, 28, and 27-year-old Tashfeen Malik were shot dead following a police chase, San Bernardino police said.
They wore "assault-style" clothing which held magazines and were armed with assault rifles and handguns during the attack at the Inland Regional Center, a facility for people with disabilities.
US-born Farook was an environmental specialist at the public health department, according to San Bernardino Police Chief Jarrod Burguan, and had been at the centre for a Christmas party with colleagues.
Mr Burguan said: "He was at the party. He did leave the party under some circumstances that were described as angry or something of that nature.
"They came prepared to do what they did, as if they were on a mission."
Bomb squad officers were also sent to the building after three explosive devices all connected to each other were discovered and destroyed.
The suspects fled the scene in a black SUV, and police later stopped a vehicle matching that description in Redlands.
Shots were fired from the vehicle and a fake bomb was thrown from the SUV during the chase, according to authorities.
Police confirmed both suspects were killed in a shootout. One officer suffered non life-threatening injuries.
A third person seen running away from the vehicle was detained, but it was unclear if they were involved in the attack.
The attack - on an auditorium packed with around 100 people - is the deadliest shooting in the US since the massacre at Sandy Hook Elementary School, Connecticut, in December 2012, when 27 people including the gunman were killed.
Brandon Hunt, who works at the centre, said a holiday party for health department workers was being held inside at the time.
The motive for the attack is unknown and an FBI spokesman told a news conference: "We do not know if this is a terrorist incident."
Terry Petit fought back tears as he said he had received texts from his daughter saying she was hiding from gunfire at the facility.
Mr Petit read a message to reporters outside the Inland Regional Center that said: "People shot.
"In the office waiting for cops. Pray for us. I am locked in an office."
Television images showed people being evacuated with their arms raised from the building, where hundreds of people work.
US President Barack Obama again called for strengthened gun control laws and stronger background checks.
He told CBS News: "The one thing we do know is that we have a pattern now of mass shootings in this country that has no parallel anywhere else in the world."
There have been more than 350 shootings this year, in which four or more people were wounded or killed in the US, according to shootingtracker.com.
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