The new rule, which will take effect next month, comes as the state looks to slow a rising number of coronavirus infections and hospitalizations primarily affecting those who are not vaccinated, though the number of new cases is still well below the peak.
At least 238,000 state employees and 2 million health care workers across public and private sectors will be subject to the new mandate, the Associated Press reported.
"We are now dealing with a pandemic of the unvaccinated, and it’s going to take renewed efforts to protect Californians from the dangerous delta variant," Gov. Gavin Newsom said in a news release announcing the new policy.
The delta variant now accounts for an estimated 80% of COVID-19 cases in California.
About 75% of eligible California residents have received at least one vaccine dose and 62% are fully vaccinated, but the number of people getting vaccinated has dropped significantly.
"The delta variant is up to 60% more infectious than the alpha strain but many times more infectious than the original COVID-19 strain," California Health and Human Services Secretary Mark Ghaly said in a written statement. "If you have been waiting to get vaccinated, now is the time."
Even with the number of coronavirus hospitalizations rising – nearly 3,000 in California up from a low of fewer than 900 in June – Newsom has appeared hesitant to restore safety measures like social distancing and mask requirements since the state began reopening last month. He's facing a recall election in September and has been criticized by his political opponents and others in the state for the way he has handled the pandemic.
Some local officials in California have already begun stepping up safety measures. Los Angeles County brought back its indoor mask requirement last week, even for people who are fully vaccinated. And in Santa Clara County, officials have said they intend to have all 22,000 county employees get vaccinated.
California isn't the only place in the U.S. where more vaccine mandates and other requirements are being added. On Monday, New York City Mayor Bill de Blasio said he would require all city employees to get vaccinated or be tested weekly.
In Missouri, St. Louis County officials also implemented a new mask mandate. And health officials in cities like Las Vegas have also recommended that everyone wear masks indoors, even if they've been vaccinated.
The Associated Press contributed to this report.