Emergency services were called to a High School in Milford, Connecticut, shortly after 7am.
The school was put on lockdown as pupils were told to stay in their classrooms.
The 16-year-old victim, Maren Sanchez, was reportedly stabbed in the throat.
She was taken to a nearby hospital where she later died.
A police officer at the Jonathan Law High School after the stabbing
Sources told the Connecticut Post the girl was attacked in a dispute over a prom date.
Police have not confirmed the report but are investigating the claim.
A 16-year-old boy has been charged with murder.
Police said the defendant was charged as a juvenile offender, but could be later charged as an adult when he appears in court on Monday in New Haven.
Officers said the attack was an isolated incident and that other students were safe.
Pupils have described an emotional scene with people crying as police and paramedics attended the incident.
The junior prom had been scheduled for Friday evening and was postponed because of the stabbing.