The Metropolitan Fire Service was called to the blaze on Edwards Court at Gilles Plains just after 11pm on Saturday.
The victim was found unconscious inside the home and was taken outside by emergency crews.
SA Ambulance Service staff performed CPR on the 74-year-old man, "who unfortunately was later pronounced deceased on scene", an MFS spokesperson said.
Fire Cause Investigation
Fire cause investigators have attended the home, but police said the incident was "not believed to be suspicious", and that a report would be prepared for the coroner.
The MFS said 16 firefighters attended the scene, where the roof had partially collapsed, and stopped the flames spreading to neighbouring properties.
It took about 25 minutes for crews to extinguish the fire, and the damage bill has been estimated at $400,000.
Separate Fire in Goodwood
Meanwhile, a separate fire at Goodwood earlier in the night has left a resident with burns and smoke inhalation, the MFS has said.
Smoke and flames were billowing from a lounge room window of the property on Hampton Street when firefighters arrived, and the resident was taken to hospital.
That blaze was extinguished within about 20 minutes and has caused $50,000 worth of damage to the property.
An MFS spokesperson said the fire was caused by cigarettes being left "unattended".
Remembering a Joyful Man
The grandson of the elderly man killed in the Adelaide house fire said the 74-year-old was a joyful man, dearly loved by his family.
Henry Fielke, 74, was found unconscious in his home on Edwards Court in Gilles Plains when emergency services arrived at 11.30pm on Saturday to find the house engulfed in flames.
Fielke’s grandson, Hayden, said he last saw his grandfather on Wednesday and said he was doing well at the time.
"He was a sensitive old man … loved to do jokes, he was a great guy,” Hayden said.
"It’s really sad what happened.”
Police do not believe the fire is suspicious. A report is being prepared for the coroner.