Mitchell was 8 of 11 from the field with 27 points. Tuttle was 6 of 9 from the field, with 21 points. He also had a team-high 10 rebounds. Marc Sonnen added 11 points for the Panthers (2-0).
Northern Iowa had a 41-38 lead at halftime, but Toledo was not done.
At the end of regulation, the score was tied at 70. Northern Iowa scored 14 points in overtime.
The game was the first-ever meeting between Northern Iowa and Toledo in basketball.
Toledo is a favorite to win the Mid-American Conference's West Division.
Maryland point guard Melo Trimble, considered a lock to leave the program before struggling in the second half last season, has withdrawn from the NBA draft and will return for his junior season.
Louisville's Chinanu Onuaku, who recently underwent a medical procedure to correct a heart rhythm issue detected during the combine, will keep his name in the NBA draft pool.
Andrew White III will return to the Nebraska men's basketball team next season after removing his name from the NBA draft.