A 16-year-old student wielding two knives stabbed and injured 21 people in the hallways of a Pittsburgh-area high school early today, officials said.
The attacker moved through Franklin Regional High School, stabbing his victims in the torso and slashing arms and faces before anyone realised what was happening, students and officials said.
Some of the injured taken to nearby hospitals were in critical condition, doctors said.
Students described a scene of panic, with the school hastily evacuated after a fire alarm was pulled.
The unidentified suspected in the attack was in police custody, said Tom Seefeld, chief of police in Murrysville, Pennsylvania.
The attacker, described by a classmate as a quiet person who kept to himself, started his rampage at around 7.13am local time (12.13pm Irish time), going along the hallways to several classrooms at the school in Murrysville, 32km east of Pittsburgh.
An armed security officer subdued and arrested the suspect with help from the principal, Mr Seefeld said.
Student Josh Frank said he did not initially realise that anyone had been stabbed, but fled when he heard screaming.
"We heard a girl scream bloody murder. Then two seniors were running down the hall and we followed them out of the school," he said.
A total of 21 people, most of them 14 to 17 years old, were transported to local hospitals, four by medical helicopters.
Several had life-threatening injuries, with nine in critical condition, hospital officials said.
The attacker used a large knife, based on the wounds suffered by at least one of his victims, said a doctor who had operated on a 17-year-old student with a large chest wound.
"Apparently it was a large knife of some sort, because it was a large injury to his abdominal wall and went through his liver, diaphragm and major blood vessels," said Dr Louis Alarcon of the University of Pittsburgh Medical Center.
"Fortunately for this young man, the knife missed his heart and his aorta."
While the United States has seen a number of large-scale school shootings in recent years, most notably the December 2012 massacre of 26 children and adults at Sandy Hook Elementary School in Newtown, Connecticut, mass stabbings are less common.
The suspect was also being treated for injuries to his hands, Mr Seefeld said.
A student at the school who witnessed the incident said she had been in several classes with the suspected attacker.
"He's kind of quiet and he keeps to himself," the student, Mia Meixner, told CNN.
"He was never mean to anyone and I don't think anyone was mean to him."
Gennaro Piraino, superintendent of the Franklin Regional School District, said the high school would be closed for the next two to three days while police conduct an investigation.