The assailant, a man in his early 20s, fired dozens of rounds through the church windows and then took his own life, officials said.
He was armed with a rifle, a shotgun and a pistol, they said.
"This was a deliberate act of violence against innocent children and other people worshiping. The sheer cruelty and cowardice of firing into a church full of children is absolutely incomprehensible," Minneapolis police chief Brian O'Hara told reporters.
The shooting occurred two days after school started at Annunciation Catholic School, a private primary school with about 390 students connected to a Roman Catholic church in a residential area in the southeast part of Minnesota's largest city.
Local TV showed parents ducking under yellow police crime tape and leading students out of the school.
Officials said the shooter did not have an extensive criminal history.
They did not provide his name and said they were trying to identify a motive.
Law enforcement was investigating multiple online videos to determine if they were posted by the shooter, according to two sources who spoke on condition of anonymity.
Local hospitals said they were treating 15 children and two adults, with many suffering gunshot wounds.
"Don't just say this is about thoughts and prayers right now. These kids were literally praying. It was the first week of school. They were in a church," Minneapolis mayor Jacob Frey said at a news conference, visibly angry.
US President Donald Trump said he had been briefed on the shooting and said the FBI was on the scene.
"Please join me in praying for everyone involved!" he said on social media.
The US Department of Homeland Security is in touch with local authorities and monitoring the situation, Homeland Security Secretary Kristi Noem said on social media.
There have been three other shootings in the midwestern city since Tuesday afternoon, including one at a Jesuit high school, that have together left three people dead and seven wounded, according to police.
Wednesday's shooting did not appear to be related to the others, O'Hara said.
Minnesota state law requires background checks for all gun sales and the state as a whole has a gun death rate below the US average, according to gun violence prevention group Everytown for Gun Safety.
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