Minneapolis Public Schools employees must either get vaccinated against COVID-19 or be tested regularly under a mandate unanimously approved by the school board Tuesday night.
The policy will take effect by Oct. 15 and extends to contractors and volunteers who work directly with students.
It comes in response to a surge of COVID-19 cases caused by the highly contagious delta variant.
"These conversations around vaccines have been happening across the nation," Minneapolis Superintendent Ed Graff said.
"The commonality across all the districts including Minneapolis Public Schools is the belief that a high vaccination rate among our staff is critical to keeping our schools open for in-person instruction and protecting our students."
The St. Paul school board approved a similar vaccination mandate earlier this month.
Minneapolis school board member Ira Jourdain offered an amendment Tuesday to also require students in the district to be vaccinated.
"I think it's the right thing to do," Jourdain said. "I'm just worried about my own kids going to school."