The shooting was reported at 10:30 a.m. on the 8000 block of North Boyd Ave.
Fresno Police said the girl was playing in the room with two other children when her 2-year-old brother walked into a bedroom holding a handgun.
Police said the gun went off and struck the girl, killing her. Investigators are treating the shooting as accidental.
The children's father was inside the house and called 911 after hearing the gunshot. The other two children in the home were not injured.
We will have more on this developing story on abc30.com and Action News Live at Six.