These federal rules identify COVID-19 as an occupational hazard. Businesses that don't comply could be fined $14,000 per infraction, and hospitals could lose access to Medicare and Medicaid dollars.
The temporary emergency rule for the private sector requires every U.S. private business that employs 100 workers or more -- from grocery stores to meatpacking plants -- to get their workers fully vaccinated by Jan. 4, 2022, and have unvaccinated workers produce negative COVID-19 test results on a weekly basis.
This impacts some 80 million Americans, or two-thirds of all U.S. workers.
The private sector rule, drafted by the Labor Department's Occupational Safety and Health Administration (OSHA), also necessitates paid-time off for employees to get vaccinated and face mask mandates for all unvaccinated workers. Employers must comply with the time-off and masking requirements by Dec. 5.
This will be the first time Washington has set a federal standard that regards a respiratory virus as an occupational hazard outside of the health care sector, essentially putting COVID in the same category as other workplace safety concerns as asbestos and dangerous machinery.
"It's the biggest thing OSHA has ever done in terms of the number of workers it will cover," said Jordan Barab, a longtime top official at the agency during the Obama administration.
The vaccine compliance deadline for federal workers, with no testing option, remains Nov. 22, while the deadline for federal contractors has been pushed back from Dec. 8 to Jan. 4.
Vaccine mandate for health care workers
In conjunction with the OSHA rule, the Department of Health and Human Services drafted a requirement for all health care workers at facilities participating in Medicare and Medicaid to be fully vaccinated.
The rule applies to more than 17 million workers at approximately 76,000 health care facilities, including hospitals and long-term care facilities, according to HHS. The requirement concerns all facility employees, clinical or non-clinical, including employees, students, trainees and volunteers.
"It also includes individuals who provide treatment or other services for the facility under contract or other arrangements. Among the facility types covered by the rule are hospitals, ambulatory surgery centers, dialysis facilities, home health agencies, and long-term care facilities," according to the Biden administration announcement.
Like the OSHA mandate, the HHS rule requires health care workers to be fully vaccinated by Jan. 4, 2022.
Biden's COVID-19 strategy
The requirements are part of Biden's aggressive new plan to try quell a pandemic that's overshadowed his presidency and hobbled the economy. At the same time, the Jan. 4 date is a nod to industry groups that insisted the administration wait until after the holidays to impose mandates in the midst of a worker shortage.
"This is good for the economy," a senior administration official told reporters late Wednesday on the rationale for the plan.
Since taking office, the Biden administration had avoided imposing nationwide vaccine mandates, focusing instead on incentives for businesses and individuals. But with the arrival of the delta variant, a surge in pediatric cases and pockets of the country remaining hesitant to get a shot, Biden's COVID strategy shifted in recent weeks.
"We've been patient, but our patience is wearing thin. And your refusal has cost all of us," Biden said of unvaccinated Americans on Sept. 9 when announcing his plan to draft the rule.
When asked whether the worker shortage was a factor in the decision, administration officials said the primary focus was on making compliance easier for workers and aligning deadlines across the private sector.
Backlash and support
Once divided on how to address the pandemic, Republican governors have united against the plan, insisting it represents dangerous federal overreach and would cripple business owners already dealing with worker shortages.
"Rest assured, we will fight them to the gates of hell to protect the liberty and livelihood of every South Carolinian," tweeted the South Carolina GOP Gov. Henry McMaster last September following Biden's announcement.
Supporters counter that many large businesses have already embraced vaccine mandates to both entice employees who want a safe workplace and end a pandemic that has hobbled the economy. They argue too that whenever employees have enacted mandates, the vast majority of workers comply.
CDC COVID-19 Transmission Levels by U.S. CountyMap not displaying correctly? Click here to open in a new window.
ABC News contributed to this report.
The video in the media player above was used in a previous report.