The call came in just before 4 a.m. on Wednesday for a fire on the 300 block of Hewitt Street, with people reportedly trapped inside.
When crews arrived, they saw heavy fire coming from a three-story house.
Officials say the victims are a young boy and girl.
There was also an adult who was at the home at the time, who was able to get out of the house, officials added.
"The adult, from what I was told, escaped the house unscathed," Deputy Fire Chief Kevin Rice said.
One firefighter was transported for burns to the back of his legs and another was treated for respiratory issues at the scene.
A neighbor tired to help put battle the fire with a garden hose, knowing there were juveniles inside, Rice said.
Firefighters said they believe the fire started on the first floor, in the living room, which quickly spread throughout the home.
It is unknown if there were working smoke detectors at the time of the fire.
Officials say the entire house is destroyed and two other homes were damaged.
Local and state fire marshals are at the scene, and the American Red Cross is helping those displaced.
The cause of the fire is under investigation.
This is a developing story and will be updated.