An 18-year-old student has been arrested over the incident.
The 17-year-old injured student is thought to be in a serious condition and is receiving treatment in at Berri Hospital.
First aid was administered by staff and paramedics.
Police were called out to Renmark High School in the Riverland region at 2.40pm local time.
The altercation involved two female students.
The school was briefly in lockdown, which was lifted once it was determined there was no risk to other students.
The crime scene remains cordoned off and is being scoured by police.
The state's Education Department said the dispute was limited to the two girls and "did not represent a specific threat to the wider school community".
Arrangements are being made to provide counselling and support for students and staff, a spokesperson for the Department said.
"An assessment is being made as to whether additional security measures are required."
