The fire appeared to have started shortly before 4 a.m. on the first floor of a three-story home used as an adult care facility, fire officials said.
Two people died on the third floor and nine others were taken to hospitals, Detroit Fire Chief Lee Moore said.
Broadcasters reported a third person died at a hospital, but Moore said fire officials were aware of only two deaths, and the hospital didn't confirm a third death.
Sophia Moss, the resident manager of the home, said she was awakened early Thursday by smoke alarms in the home and went door to door screaming at residents to wake up and get out of the house. She left her second-floor bedroom to alert residents on the first floor and then went back upstairs.
``I couldn't make it up to the third floor,'' Moss said. ``I wanted to go back in and I couldn't.''
One resident was able to carry a wheelchair-bound man out the back door, Moss said. Witnesses urged others to jump from the windows to escape.
The home, which owner DelMarie Headd said has operated for 10 years, was extensively damaged in the blaze. She said she was trying to arrange accommodations for the surviving residents, who were either Medicaid or Social Security disability recipients.
``I'm not going to leave them out,'' Headd said. ``I wish I could say that about all of them.''
Fire investigators were still trying to determine the cause of the blaze.