The measures include a vaccine mandate for millions of federal government workers and come as Mr Biden faces pressure to combat a surge in cases.
Over 650,000 Americans have died with Covid-19 and hospitals are at capacity.
The president had promised a “summer of freedom” from the virus, but the Delta variant has seen infections surge.
In an address at the White House on Thursday, Mr Biden directed the US Department of Labor to require all private businesses with 100 or more staff to mandate the jab or request proof of a negative coronavirus test from employees at least once a week.
The order will affect about 80 million workers.
“This is not about freedom, or personal choice, it’s about protecting yourself and those around you,” the president said as he unveiled the six-point plan.
Nearly 17 million other healthcare workers at facilities receiving federal benefits will also face the same requirements, he said.
The president’s plan uses the full force of his executive power to mandate the jab for unvaccinated Americans.
Some of his initiatives address common concerns of Americans who have yet to get the vaccine – such as not wanting to miss work to get the jab or recover from side effects.
The president said that requirements that large businesses provide paid time off for workers to get vaccinated will be unveiled in the coming weeks by the Occupational Safety and Health Administration (Osha).
Businesses that do not comply with the new rules may face thousands of dollars in fines per violation.
A separate federal mandate, which the White House says will impact some 2.5 million government workers, supersedes Mr Biden’s earlier order that permitted government employees to undergo regular testing if they did not wish to be vaccinated. Now workers that refuse the jab may be fired.
Overall, the rule now requires that about two-thirds of all US workers be vaccinated. (Courtesy BBC)