It happened in January at Giles School and Sixth Form Centre in Old Leake, Lincolnshire, a visual arts specialist.
The Health and Safety Executive is investigating and safety warnings are being circulated to other schools.
The Giles School's head teacher, Chris Walls, said in a statement: "I can confirm that a serious accident did occur in our art department at the end of January and that the Health and Safety Executive are involved.
"They are in the initial stages of their enquiry into this accident and we do not wish to make any further comment until this has been completed."
The executive told the BBC News website that the girl had lost her thumbs and most of her fingers.
The warning is now circulating in safety bulletins distributed to schools by local authorities.
It was sent out by the school science advisory service, Cleapss.
"In the incident a girl was mixing plaster of Paris with water by hand, intending to make a plaster cast of her hand," it said.
