A 16-year-old American student walked from classroom to classroom randomly stabbing 19 students and a security guard in a bloody rampage at a Pennsylvania high school, officials say.

Murrysville police chief Thomas Seefeld said at least four students remain in hospital in a critical condition following the shocking assault at  Franklin Regional High School.

The 16-year-old boy walked down a hallway flashing two knives, stabbing fellow pupils and the guard as they began arriving for what should have been a routine school day shortly after 7am, Seefeld said.

It is not clear what prompted the attack by the boy, who is being treated for a hand injury, in which 19 students and one male security guard were injured, mostly in the chest and stomach.

The school principal and another member of staff tried to overpower the suspect who was then arrested, Seefeld said.

Doctor Mark Rubino at Forbes Regional Hospital said he expected everyone to survive despite what he called “deep penetrating” stab wounds.

The knife wounds, most of them to the lower abdomen, caused significant injuries to internal organs, Rubino said.

Three of the victims were still in surgery and the other five were still being evaluated, he told reporters.

“Three of the patients had severe injuries and are still in the operating room right now. And two of them are in critical condition, but they have stabilised,” Rubino said.

The other five that we had are still being evaluated, of whom one or two may require further surgery, he added.

Dan Stevens, a spokesman for Westmoreland County emergency management, told AFP that the teenage victims are aged 14 to 17 and were attacked in “numerous classrooms and hallways” of the school.

Police said the victims were found in multiple locations because they were following the correct drill to run as far away as possible in the event of an emergency.

Seefeld praised school staff, who worked in close coordination with police.

“It is my opinion that today as unfortunate as it is… I think that it could have been a lot worse if there was not immediate interaction that occurred,” he told reporters.

Pennsylvania media reported parents and former students believed the school generally did a good job of keeping students safe. It does not have metal detectors but does spot searches when security officials deem it necessary.

“I think the school reacted as fast … as possible,” Rich Nickel, whose daughter, Jenna, 16, is a sophomore, said.

“It’s obviously a (lone) individual’s act.”

– with AAP