The fire was reported around 2:30 a.m. in the 200 block of Jeffrey Street.
A 78-year-old man was rescued from the home and is hospitalized in critical condition with severe burns and smoke inhalation.
Authorities say it was a challenging situation for rescuers. They were hampered not only by the hoarding conditions inside, but also by a partial collapse.
The body of the rescued man's wife was found on the second floor. His 30-year-old daughter and 11-year-old granddaughter were discovered together on the first floor.
Chester Mayor Stefan Roots visited the scene and expressed concern for the man who survived.
"He won't have a home to come back to, which is also sad, if he survives his burns," said Mayor Roots.
Neighbors also shared their worries as the scope of the loss became clear.
"I hope God is with him and he gets through that," said William Clark.
There was no immediate word on the cause of this fire.