About 1,100 pupils have been affected by teachers going on strike in what may be the first ever industrial action at an independent school.
Some 50 staff at Newcastle-under-Lyme School in Staffordshire have walked out after the head of English was sacked, partly due to poor exam results.
A meeting on Friday between unions and school governors failed to reach an agreement to get Peter Cash reinstated.
The school said it was closed but about 40 staff had come in to work.
In a statement, the school said it wanted to resolve the situation as quickly as possible.
"Our main concern is to prevent any further disruption to our pupils' education. Our focus is to return to our normal routine," it said.
The school said a meeting was expected to be held later with staff, who are members of the Association of Teachers and Lecturers (ATL) and the National Association of Schoolmasters Union of Women Teachers (NASUWT).
Mr Cash was dismissed in December due to poor exam results, the ATL said.
Acting Principal Andrew Jeffreys said poor exam results were "a factor" in the sacking of Mr Cash but refused to comment any further.
Mary Bousted, from the ATL, said: "ATL continues to fight to get Mr Cash reinstated as head of English.
"We don't believe there are any major issues to prevent this from happening.
"We want this issue resolved as speedily as possible to avoid doing further damage to the school and pupils' education."
Brian Cookson, from the NASUWT, said the industrial action was a last resort and he could not remember a previous occasion when strike action had been taken at an independent school.
He said: "All teachers take such action seriously and very much regret having to be in that position and I would say in the independent sector that is even greater."