The Asiana Airlines flight from Seoul, South Korea, came to rest at the side of the runway with a plume of thick black smoke billowing from the hull and debris strewn across the tarmac. The plane is thought to have crashed as it touched down at about 11.30am local time, Laura Brown, a spokeswoman for the Federal Aviation Administration, said. Passengers described how the pilot appeared to overshoot the runway.
The San Francisco Fire Department told media that two people had died and 61 were injured.
Passengers were forced to jump down emergency slides to escape the plane, which lost its tail and much of its roof. Fire crews on the scene extinguished the blaze, which had burned through the cabin ceiling. Asiana said that there were 291 people on board, including a group of South Korean schoolchildren.
Rachael Kagan, a spokeswoman for San Francisco General Hospital, said 10 critically injured people had been taken there, including two children, six women and four men. She said most of them spoke only Korean.
Passenger David Eun called the crash "surreal" on Twitter. He wrote: "Fire and rescue people all over the place. They're evacuating the injured. Haven't felt this way since 9/11."
Anthony Castorani witnessed the crash from a nearby hotel. "You heard a pop and you immediately saw a large, brief fireball that came out from underneath the aircraft," he said.
Ying Kong, of Albany, New York, who was waiting at the airport for her brother-in-law, Fawen Yan, 47, from Richmond, California, said he telephoned her after surviving the crash to say it had been "really smoky and scary". "He feels it difficult to breathe, but he's OK," she said. She added: "He said a lot of people had to run. He said some people got hurt."
Lynn Lunsford, a spokesman for the Federal Aviation Administration (FAA), said the plane was Flight 214. Air traffic at the airport was halted after the crash, which took place under sunny skies with only a slight breeze.
The Asiana flight departed from Seoul at 5.04pm Korean time and touched down in San Francisco at 11:28am PDT, according to FlightAware, a website that tracks flights. The flight lasted 10 hours and 23 minutes, it said.
The National Transportation Safety Board said on its Twitter feed that it was sending an investigative team to the scene.
Boeing expressed concern for those on board the flight and added that it will provide technical assistance to the NTSB as it investigates the accident.