The member of staff at Corpus Christi Catholic College, in Neville Road, Leeds, was fatally injured this morning.
West Yorkshire Police detectives said a 15-year-old boy was arrested in connection with the incident and is in custody.
Detective superintendent Simon Beldon said there was no ongoing risk to pupils or staff and that the school was "continuing to operate as normal".
He said: "The situation is under control and officers, including safer schools officers and members of the local neighbourhood policing team, are currently at the school and are liaising closely with staff.
"The rest of the school is continuing to operate as normal and we would ask that parents do not attend the site unless directly requested to do so by the school.
"Our inquiries are at a very early stage but the full circumstances of this incident will obviously be the subject of a full and thorough investigation."
Police were called to the school at 11.48am after they were contacted by the ambulance service following a report that a member of staff had been stabbed.
The woman was taken to hospital for treatment but was subsequently pronounced dead, police said.
A 15-year-old boy, a pupil at the school, has been arrested in connection with the incident and is currently in custody.
There are nearly 1,000 pupils on the roll aged between 11 and 16, according to the school's website.
It also has "a strong Christian and community ethos".
The website adds: "The school has a very good pastoral structure, which it is committed to keeping and teachers receive very good back-up support."