Several media outlets, including the Detroit Free Press, WDFN-AM, Detroit, Fox Sports and ESPN, said Millen's tenure as the Lions' leader ended during a meeting Tuesday night.
The Free Press said it was unclear whether Millen resigned or was fired.
Detroit has started this season 0-3. Last year, the Lions were 6-2 halfway through the 2007 season but lost seven of their last eight games and missed the playoffs for the eighth consecutive season. The 7-9 record in 2007 was the best of Millen's tenure.
Millen, 50, in 2001 was made Lions president and general manager. Although he had no player personnel experience, he was highly regarded as a linebacker in 12 seasons. He was a member of four Super Bowl winning teams.
"I have relieved Matt Millen of his duties effective immediately," said Lions Owner and Chairman William Clay Ford in a statement on the team's Web site late Wednesday afternoon. "I believe that this decision is in the best interest of this organization. I appreciate Matt's efforts."