Local police said the victims were being treated for injuries at Amman Valley School in Ammanford, Carmardenshire, about 100km from the Welsh capital Cardiff.
“Three people – two teachers and a teenage student – have been taken to hospital with stab wounds,” said police spokesman Ross Evans.
“A teenage girl was arrested on suspicion of attempted murder and is currently in police custody,” he said.
The school, which has almost one and a half thousand students aged 11-18, was closed.
Two air ambulances and a line of police cars were seen near it.
Police said they were aware that footage of the incident was circulating on social media. One video reportedly shows the aftermath of a knife attack.
Welsh First Minister Vaughan Gething said on the X social network in English and Welsh that he was “shocked to hear the news of the serious incident” in Ammanford.
He also thanked the police and emergency crews for their response.
Prime Minister Rishi Sunak said he was shocked by the news.
“I want to thank the police and emergency services for their ongoing response and my thoughts are with all those affected,” he said.
