"This morning, a mother showed up with a knife and stabbed a 34-year-old teacher in front of her students, for reasons that will be determined by the investigation," Albi prosecutor Claude Derens told AFP.
"When I arrived at the scene they were trying to revive her. She was in cardiac arrest in her classroom," he said.
President Francois Hollande immediately sent Education Minister Benoit Hamon to the school to take charge of the government response.
The stabbing took place as morning classes began at Albi's Edouard Herriot primary school, which is attended by 284 students aged from three to 11.
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No further details were immediately available and a press conference was planned for this afternoon.
A spokesman for Hamon said he was on his way to the school to show his support, saying the education minister "is deeply shocked by this crime, which plunges the end of the school year into mourning."
The incident comes amid concerns in France over assaults by parents on teachers, with a study released in April saying nearly half of primary school principals had been verbally or physically abused by parents.