Between 30,000 and 40,000 mink were set loose from a farm that raises the animal for pelts, according to the Stearns County Sheriff's Office.
The mink, raised at Lang Farms near Eden Valley, Minn., are worth more than $750,000, the agency said in a statement.
Sometime overnight between late Sunday and early Monday, someone dismantled part of a fence surrounding Lang Farms' barns and let all the mink free from their cages, the statement said.
The animals were released near wildlife management and wilderness preservation areas and they could harm native wildlife, officials said.
Lang Farms is asking residents to call them so "experienced mink handlers" can recapture the animals.
"Because these mink were domesticated they will not survive in the wild, though some mink may survive initially and may be loose in the area," the sheriff's office said.
Minnesota is a national leader in mink-pelt farming.
The industry is historically a target for animal-rights activists who decry the practice and conditions in which the animals are raised.
In 2013, activists let loose some 450 mink from a farm in southeastern Minnesota in an incident that appears similar to the latest one in Stearns County.