A woman and three children were rescued after crews were sent to Deevale Road in Kincorth at 09:35 on Saturday.
Police said the child and a 39-year-old woman suffered serious injuries and all four were taken to hospital.
All four, including a 12-year-old girl and another five-year-old girl, were taken to Aberdeen Royal Infirmary.
An investigation is underway to establish the cause of the fire.
Insp Finn McPhail said: "We are currently treating the fire as unexplained and our investigation is at a very early stage.
"I would urge anyone with information that could help, or anyone who was in the area at the time and saw anything, to contact police on 101."
A Scottish Fire and Rescue Service (SFRS) spokesman said: "The caller reported being trapped by smoke on the first floor of the two-storey house and officers at Operations Control provided survival advice over the phone while directing frontline crews.
"All four casualties were passed to the care of paramedics and taken to hospital by ambulance.
"SFRS crews continued working to clear smoke from the property using a positive pressure ventilation fan and they checked a neighbouring home for any smoke travel.
"Four fire engines and a support vehicle were sent to the scene and specialist officers from a Fire Investigation Unit will work to establish the circumstances surrounding the incident."
Two people, including a five-year-old girl, have been seriously hurt in a house fire in Aberdeen.