Gardenhire, who turns 60 on Tuesday, spent 13 seasons, from 2004-2014 managing the Twins -- the Tigers American League Central division rivals.
He compiled a 1,068-1,039 record with the Twins and is one of 10 managers in baseball history to win 1,000 or more games with a single club. He was the 2010 AL Manager of the Year and was the runner-up on five occasions, but was sacked after four straight seasons of 90 or more defeats.
He spent 2017 as bench coach for the Arizona Diamondbacks.
"After an extensive search, we are confident 'Gardy' is the right person to lead our ballclub in our pursuit of World Series championships," general manager Al Avila said in a statement. "Ron has extensive managerial experience at the major league level and has a proven track record of player development."
Gardenhire said he "couldn't be more thrilled" after inking a three-year contract with the Tigers.
"After managing against the Tigers for so many years, I know first-hand what a great baseball town Detroit is and that the fans here are some of the most passionate in all of sports," he said.