The fire broke out just before 5 a.m. on the 2400 block of North Myrtlewood Street.
Firefighters arrived to find smoke throughout the two-story row house.
Among the injured adults were the parents of the children. Officials said the father was in critical condition.
One of the adults even jumped out of a window to escape the flames.
Officials would not confirm the ages of the children who died. A total of 60 firefighters, medics and support personnel responded to the scene.
The fire was placed under control at 5:18 a.m.
"Companies are in the process of overhaul operations to see what we can salvage at the property," said Assistant Fire Chief Richard Davison.
Investigators are on scene looking into the cause of the fire.