Uber said it is suspending self-driving car tests in all North American cities after a fatal accident.
A 49-year-old woman was hit by a car and killed as she crossed the street in Tempe, Arizona.
While self-driving cars have been involved in multiple accidents, it is thought to be the first time an autonomous car has been involved in a fatal collision.
Uber chief Dara Khosrowshahi said the death was "incredibly sad news".
Police said the accident happened Sunday night while the car was in autonomous mode. A human monitor was also behind the wheel.
Police said the woman, Elaine Herzberg, had not been using a pedestrian crossing. She was taken to a local hospital, where she died.
The US National Highway Traffic Safety Administration and the National Transportation Safety Board said they were sending teams to Tempe.
'Wake up call'
Companies including Ford, General Motors, Tesla and Waymo are investing heavily in research to develop self-driving cars, which are often characterised as the future of the industry and hailed as a way to reduce traffic accidents.
Many states across America have welcomed the tests in the hope of keeping themselves at the forefront of new technology.
However, there have been warnings that the technology is being deployed before it is ready.
Anthony Foxx, who served as US Secretary of Transportation under former President Barack Obama, called the accident a "wake up call to the entire [autonomous vehicle] industry and government to put a high priority on safety."
More than a dozen states in the US allow autonomous vehicles on the roads to some degree. Officials typically require a person to be on hand either in the car or remotely in case something goes wrong, according to the Center for Automotive Research.
The US is working on national safety guidelines for such vehicles.