Ausmus, 48, and his coaching staff will remain in their current positions through the end of the season, according to general manager Al Avila.
The Tigers entered Friday's games in fourth place in the American League Central with a 62-91 record, and will finish with their fewest wins in a season under Ausmus.
Avila made the announcement at Comerica Park ahead of the Tigers' game against the Minnesota Twins.
"As we transition the ballclub in a new direction, I feel it's best we have a new approach and a fresh start with the manager position," Avila said in a statement. "Brad has done an admirable job under, at times, difficult circumstances, especially this season, and we appreciate his professionalism and dedication to the Tigers the past four years.
"Our search for a new manager is underway. We plan to keep an open-mind in considering current members of the coaching staff for positions in 2018, but that will be in conjunction with the manager we hire."
Ausmus was named the 37th manager in Tigers history on Nov. 3, 2013. He led Detroit to an American League Central Division title in his first season as manager in 2014, its only postseason appearance under Ausmus.
During his four-year tenure as manager, the Tigers have posted a 312-325 (.490) record.
Ausmus was a former catcher for the Tigers, playing in 1996 and again from 1999 to 2000.