The older boy was playing with his mother's loaded gun at the family's third-floor apartment in New Jersey when he accidentally shot his brother in the head, Connie Jackson, a city spokeswoman, said.
The boy was taken to University Hospital in Newark where he was pronounced dead yesterday, a hospital spokesperson was quoted as saying by CBS News.
The boys' mother, 22-year-old Itiyanah Spruill, was arrested later and charged with endangering the welfare of a child and a weapons violation. She was being held on USD 310,000 bail.
"This is crazy because they should have a safe place," Vania Limage, a neighbour, was quoted as saying.
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"Because that's been going on in the news over and over, where you hear about those incidents going on. So people should not have a gun around a four-year-old and a six-year-old," Limage said.
City police and investigators with Essex County's Major Crimes Task Force were investigating the shooting.
The incident was the latest in a slew of shootings in the US involving toddlers.
A 5-year-old girl in Detroit last month died after she shot herself with a gun she found under her grandmother's pillow.