Fire officials said those killed lived in two third-floor apartments in Newark's Vailsburg neighborhood, near Irvington.
A 3-year-old girl and her 4-year-old brother died in a back apartment, fire Capt. John Brown said. Their mother and father escaped the blaze with two other children, and all four were hospitalized with non-life-threatening injuries, Brown said.
A father and his 6-year-old daughter and teenage son died in the other apartment, fire officials said. The ages of the father and the son were not immediately known. Officials had not released any of the victims' names by Friday evening.
Fire officials said the blaze began in a vacant building next door.
The fire started just before 2 a.m. Friday and quickly escalated, damaging four other buildings and displacing about 15 people. Red Cross officials said they were assisting four displaced families.
Neighbors told the New York television station WABC-TV that the vacant building had recently been boarded up after numerous complaints of squatters and illegal activity.
Officials declined to comment on the cause of the fire, saying it was still under investigation.
Mayor Cory Booker said the deaths were a tragedy for the state's largest city.
"My deep condolences go out to the victims and their families who are suffering because of this terrible fire," Booker said in a statement. "This is a tragic loss for all those affected and our city as a whole."
The mayor tweeted a link to a Facebook page set up to receive donations for the affected families.