He then turned the gun on himself, police said.
Police chief Jarrod Burguan described the incident as a suspected "murder-suicide" attempt.
Mr Anderson (R) killed his estranged wife Ms Smith (L) and an eight-year-old boy
The gunman, named as 53-year-old Cedric Anderson, had gained entry to the school as a visitor and kept his weapon concealed until he opened fire in the classroom where 15 children with special needs were being taught, authorities said.
He killed his wife Karen Elaine Smith and fatally wounded eight-year-old Jonathan Martinez, who was airlifted to hospital but later died.
A nine-year-old pupil remains in hospital in a stable condition, the Los Angeles Times reported.
Mr Burguan tweeted shortly after the incident that the suspect was "down" and there was "no further threat". The school was immediately evacuated.
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10/04/2017
23:14
The shooter fatally shot the teacher at the school before turning the gun on himself. The two children who were shot during the incident were taken to a nearby hospital for treatment.
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22:39
At least four people, including a teacher and two students, have been shot at an elementary school in San Bernardino, California. The incident is believed to have been a murder-suicide, according to police.
The shooting occurred in a classroom at North Park School. Along with the four victims, the suspect is believed to be down as well, according to San Bernardino Police Chief Jarrod Burguan.
The two students were transported to the hospital via helicopter, a spokesperson for the San Bernardino City Unified School District told KCBS.
The fire department has set up a triage to assess and treat victims at the scene.
North Park, Cajon and Hillside Elementary Schools are on lockdown, while the San Bernardino campus of California State University is under a shelter-in-place order.
This is the second mass shooting in the southern California city in since December 2015. In that incident, which was later categorized as an act of terrorism, a married couple opened fire on a holiday party for the husband’s work, killing 14 and injuring 21.
***
22:24
At least two people have been shot in a suspected "murder-suicide" at a primary school in southern California, police say.
North Park Elementary in the city of San Bernardino is on lockdown after the attack in a classroom, say officials.
Two students were transported to hospital, said San Bernardino Police Chief Jarrod Burguan.
Police are working with emergency workers and fire crews at the scene, Mr Burguan added.
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