Minneapolis Fire Chief John Fruetel said three children died at the scene of the pre-dawn fire in north Minneapolis. The medical examiner's office did not immediately release any information about the two other victims.
Other residents were injured and taken to area hospitals. The conditions of the injured were not immediately released.
Asst. Fire Chief Cherie Penn said in an email that one of the more than 40 firefighters who responded to the scene was being treated at a hospital for a minor injury.
Fruetel said firefighters encountered heavy smoke and fire on the second and third floor of the duplex as they searched the building for victims and survivors.
Fire officials said 15 people lived in the duplex.
It took fire officials about 2½ hours to put out the fire. There was a smell of burnt wood in the air hours after the blaze, as firefighters continued to move in and out of the building. The house's front exterior appeared mostly intact aside from blown out and broken windows and doors.
But when looking into the windows, the interior looked blackened and charred with broken ceiling beams and torn insulation.
The cause of the fire was being investigated.
Associated Press Writer Gretchen Ehlke contributed to this report from Milwaukee.