The move, the most sweeping by any USA state so far, came amid warnings that the coronavirus threatens to overwhelm the region's medical system.
Newsom said the order will remain in effect "until further notice", although he does not believe it will last "many, many months".
California has 675 confirmed coronavirus cases and 16 deaths, according to the state's official tally.
"It is at times like this when we are filled with anxiety, a great deal of uncertainty, and it is understandable that people have a scarcity mindset, as seen in some of the decisions people make with purchases", Newsom said in a address and question and answer session on Facebook, Saturday night.
Several counties in the Bay Area, including San Francisco, had already imposed similar stay-at-home measures earlier in the week.
This previous week, Newsom stated the state had began to obtain medical gear from the Strategic Nationwide Stockpile.
Newsom on Thursday also wrote a letter to Congress requesting "more than $1 billion in initial funding" for California to tackle the pandemic.
"Our state and health care delivery system are significantly impacted by the rapid increase in COVID-19 cases".
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Mr Johnson also spoke about an anti-body test which would hopefully show who had already had coronavirus - something the prime minister said could be a "game-changer".
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The Democratic governor said parts of the state were seeing infection rates double every four days.
Mr Newsom said Los Angeles, which has a population of more than 12 million people, was likely to be "disproportionately impacted" by the pandemic in the coming weeks.
A staff member disinfects the handles of shopping trolleys outside a Costco supermarket in Los Angeles, the United States, March 14, 2020.
"But we're seeing upwards of 800 people now and more than 900 at dinner".
The order came several days after six counties in the Bay Area instated a "shelter in place" order that put similar restrictions on the almost 7 million residents in those counties.
In a press conference within the same hour when Newsom gave a statewide stay-at-home order, Los Angeles Mayor Eric Garcetti emphasized that this is a health emergency and nobody is on lockdown, insisting that "this is not a shelter-in-place".
The hearing was related to a lawsuit filed by a local group of business owners, residents and others concerned about the squalid conditions facing homeless people living on the streets or in their cars in the city's downtown.
The order of the county was announced after a second person died for coronavirus in the county Thursday, and an additional 40 cases were reported in the county, bringing the total to 230 patients.