In a statement issued Wednesday afternoon, Michigan athletic director Warde Manuel said the school wanted to give as much advance notice as possible.
The weather forecast for Ann Arbor has slowly deteriorated throughout the week, with the latest projections calling for rain and temperatures in the 40s.
"We want to ensure the safety of our fans as well as the student-athletes and staff," Manuel said.
Michigan had previously moved up the start time for the event, from 7 p.m. to 5:45 p.m., which was going to be a controlled scrimmage opposed to a traditional game format.
The game will not be made up, and the team will likely practice indoors, as it has all spring long.
Michigan joins Wisconsin and Iowa State in choosing to cancel their annual spring football games for weather.
"We are disappointed for our fans and players' families that this opportunity to see our team compete at Michigan Stadium will not be possible due to weather conditions," Michigan coach Jim Harbaugh said in the statement.
"We made a decision that was in the best interest of our fans, student-athletes and volunteer staff needed to organize this event."
The Wolverines will practice on Thursday, their 10th of the spring schedule, which concludes April 24.