The San Francisco 49ers and Jim Harbaugh mutually agreed to part on Sunday, paving the way for the 51-year-old to coach Michigan.
San Francisco made the announcement after the 49ers (8-8) ended the 2014 NFL season with a 20-17 victory over the Arizona Cardinals at Levi's Stadium in Santa Clara.
Sunday's news comes after college outfit Michigan - where Harbaugh was a student - made an official approach for his services during the week.
Harbaugh, who had a year remaining on his contract, departs the 49ers with a 49-22-1 overall record (5-3 post-season) in four years in San Francisco.
"Jim and I have come to the conclusion that it is in our mutual best interest to move in different directions," said 49ers CEO Jed York.
"We thank Jim for bringing a tremendous competitive nature and a great passion for the game to the 49ers.
"He and his staff restored a winning culture that has been the standard for our franchise throughout its history.
"Their commitment and hard work resulted in a period of success that should be looked back on proudly by our organization and our fans. We wish Jim and his family all the best."
Harbaugh endured a turbulent fourth season in charge of the 49ers amid talk of player unrest and a feud with general manager Trent Baalke.
The dual National Football Conference (NFC) champion is reportedly set to earn $48million over six years in Michigan.
"For the last four seasons I have had the great privilege to coach one of the storied franchises in the history of football," said Harbaugh.
"We accomplished many great things together as a team during this period, which is a tribute to the incredible efforts of some of the most dedicated players and coaches in the NFL. I will miss competing alongside this group of players and coaches, I have the utmost respect and admiration for their hard work and support.
"It has been my honour to share the sideline with these mighty men. I will always appreciate and remember fondly, the passion and support of our faithful fans, and want to express my particular thanks to them."