The blaze broke out around 8 a.m. in the city's working-class Kensington neighborhood, north of downtown. The children and adults were trapped because security bars were installed in the windows, Ayers said.
"The bars usually keep us from getting in and keep residents from getting out," Fire Commissioner Lloyd Ayers said. "There were so many things that came together to spell disaster."
Investigators did not immediately determine the cause of the fire, and there was no word whether the house had smoke detectors.
It took just nine minutes to extinguish the one-alarm blaze, Ayers said.
Authorities were unsure about initial reports that one adult was injured leaping from a second-story window.
Irene Weal, who lives across the street and called 911 to report the blaze, said the family lived in the home on the block of well-tended brick and stucco houses for a little more than a year.
"It could have happened to my kids," she said.
Neighbors said the victims were a boy and four girls ranging in age from 6 months to 6 years old. Three were siblings and the other two were their cousins, neighbors said.
The two adults in the house, believed to be the parents of the three siblings who died, were hospitalized for treatment of burns and smoke inhalation, police said.