Fire crews were searching for possible victims in the debris at the private school, officials said. One witness said two men yelled “gas” shortly before the blast.
Three people on the roof needed assistance getting down.
The Minneapolis Fire Department initially said one person was killed. But it later tweeted the death was not confirmed.
Authorities said early indications are the blast was caused by a ruptured gas line.
Becca Virden, a spokeswoman for CenterPoint Energy, said crews were called to the area of a school boiler room to assist.
The Christian school said there was a gas leak and explosion at its multistory Upper School, which houses grades 9-12. The academy has about 825 students in grades Pre-K through 12, housed on two campuses. The 2017-18 school year is set to begin August 23.
Video broadcast by CNN affiliate WCCO showed smoke and flames rising from the debris.
Jack Mahler was warming up for a soccer practice nearby when he heard two sprinting men yelling “gas!” and “get out!” Shortly after, there was a huge explosion that knocked him off his feet, he told WCCO, “and then it was just kinda chaos from there.”
John Barron, who lives across the street from the academy, told the station that the blast shook his windows and startled his dogs.
“I saw that where the building used to be one continuous building, (it) now had a gap,” he said. “I could see sunlight all the way through to the other side.”
Gov. Mark Dayton pledged resources for first responders. “I thank the many firefighters, paramedics, and law enforcement officers who rushed to the scene this morning, and who are working still to ensure the safety of our children, adults, friends, and neighbors,” he said in a statement.
This story has been updated to reflect the latest information from fire officials.
By Phil Gast and Eric Levenson, CNN