Robotics start-up Nuro plans to start its driverless delivery operations as early as next year.
It previously tested its R2 vehicles in the state in April, but the permit will let it charge people for its service.
The firm's vehicles will be limited to 35mph (56km/h), and will be restricted to operating in "fair weather" conditions.
“Issuing the first deployment permit is a significant milestone in the evolution of autonomous vehicles in California,” said California Department of Motor Vehicles director Steve Gordon.
“We will continue to keep the safety of the motoring public in mind as this technology develops.”
Nuro was founded by two former Google engineers and has funding from Japanese firm Softbank.
Its vehicles are designed to operate without a driver or passengers in them.
The R2 uses radar, thermal imaging and 360-degree cameras to direct its movement. And it lacks a steering wheel, pedals or side-view mirrors.
The vehicle has an egg-shaped frame that is smaller than most cars in the US. It also has two temperature-controlled compartments for deliveries. Doors raise up to reveal the items once a code has been entered by the recipient.
During a previous trial in Houston, Texas, in February, the R2 delivered pizza for Domino's Pizza, groceries from supermarket chain Kroger and goods for Walmart.
Even so, one transport expert said safety issues would continue to be a concern.
"It will be very limited to begin with while the technology is thoroughly evaluated," said Prof David Bailey from the University of Birmingham.
"So, for example, the vehicles will only be allowed on 'surface streets' with their speed limited to 35mph, and the smaller Nuro delivery bots will be limited to just 25mph.
"It's essentially a limited trial, but still a significant step towards a driverless future."
In October,driverless taxis began operating in Phoenix, Arizona, as part of Google's Waymo service.
A similar service, backed by the online tech and retail giant Alibaba, is currently being trialled in China's biggest city, Shanghai.
They mark just two of numerous trials involving various autonomous vehicles across the world.