Freeman fills the vacancy left by Clark Lea, who left Notre Dame to become head coach at Vanderbilt.
Freeman, who will also work with the linebackers at Notre Dame, had been the defensive coordinator and linebackers coach at Cincinnati since 2017 and helped the Bearcats to its 9-1 record this season, climbing to No. 8 in the rankings.
"As we looked into finding someone to run our defense, it was important to find the right fit for our program, and Marcus and his family are just that," Notre Dame coach Brian Kelly said in a statement. "He has had great success on the field, both running a defense and in his direct work with his linebackers. Additionally, he is considered among the elite recruiters in the coaching ranks.
"The work Marcus has done elevating the programs he has been a part of speaks for itself, but equally as important is the exceptional work he has done in building relationships with his staff and players. Marcus was our top choice to become our next defensive coordinator, and we are pleased he and his family will be joining us at Notre Dame."
Freeman's defense ranked No. 13 in total defense and yards allowed per game, No. 4 in yards allowed per play, No. 14 in rush yards allowed per game and 39 in pass yards per game this season.
With past experience at Purdue and Ohio State, Freeman has spent much of his career in the Midwest and is widely regarded as an excellent recruiter throughout his career.
The 34-year-old Ohio native is joining a Notre Dame team that will lose star linebacker Jeremiah Owusu-Koramoah, cornerback Nick McCloud, defensive linemen Adetokunbo Ogundeji and Daelin Hayes and safety Shaun Crawford to the NFL draft.