The blaze broke out just before 1:30 a.m. on the 300 block of Bustleton Pike.
A person driving by spotted the flames and called 911.
The family of six scrambled to escape from inside the burning home.
"They were able to exit a second floor window onto a first floor roof and they were able to jump from the first floor roof to their safety. All four children were either handed down or jumped into the arms of their parents," Northampton Township Fire Chief Adam Selisker said.
Emergency crews sent the children to St. Christopher's Hospital for Children.
The two adults were taken to Temple University Hospital.
Fire officials say they suffered smoke inhalation and some had broken bones from jumping to safety.
Bill Colligan lives behind the 300 block of Buselton Pike and woke not to flames, but the smell of smoke
"It was a heavy smoke, a toxic smoke, it smelled like plastic burning," Colligan said.
An estimated 30 to 40 firefighters responded.
Investigators believe the fire began on the first floor.
"We did have a pretty strong wind condition in the beginning of the fire. We were able to overcome that. We were able to extinguish the fire in about 20 to 25 minutes," Selisker said.
A woman in her 80s lives in another home on the property connected by a breezeway, but she got out in time and wasn't injured.
The house where the fire originated is a total loss.
"I'm happy they were able to get out. I heard they have some broken bones and things, but at least they're out," Colligan said.
No firefighters were injured.