The mayor says negotiations with employee unions are ongoing, but a detailed announcement will be made in the coming days.
"We have to absolutely have to have a vaccine mandate," Lightfoot said Wednesday. "It's for the safety of all involved, particularly members of the public who are interacting with city employees on a daily basis."
The mandate will impact about 33,000 city workers.
Lightfoot's announcement comes on the heels of an announcement Friday by Cook County Board President Toni Preckwinkle that all employees in her office would need to be fully vaccinated by October 15.
Also on Monday, a mask mandate for public indoor spaces went into effect in Cook County as COVID cases continue to surge.