The 10-foot bronze statue was pulled from its granite base by several dozen people led by a Minnesota-based Native American activist outside the state Capitol, documented by news photographers and television camera operators.
"It was the right thing to do and it was the right time to do it," the activist, Mike Forcia, told Reuters in apparent reference to more than two weeks of protests over the May 25 death of a 46-year-old black man, George Floyd, under the knee of a Minneapolis police officer.
Native American activists have long objected to honoring Columbus, saying that his expeditions to the Americas led to the colonization and genocide of their ancestors.
Saint Paul neighbors Minneapolis, and the two are commonly referred to as the Twin Cities.
Forcia said he was advised by a Minnesota state trooper that he could expect to be arrested in the coming days and charged with criminal destruction. A city crew removed the statue, which was broken at the base.
According to a website for the Capitol, the monument was created by sculptor Carlo Brioschi and dedicated in 1931 as a gift to the city from Italian-Americans in Minnesota.
On Tuesday, a monument to Columbus erected in Richmond, Virginia, in 1927 was vandalized and thrown into a lake. In the early hours of Wednesday in Boston, the head of a statue of the explorer was removed and broken.
In Washington, US House of Representatives Speaker Nancy Pelosi urged Congress on Wednesday to remove from the US Capitol 11 statues representing Confederate leaders and soldiers from the Civil War.