Police say one student is in custody and is being questioned.
The stabbing happened around 8:30 a.m. in Wednesday at Carrick High School.
Two students were transported by Pittsburgh EMS with stab wounds to their abdomens, according to police. A third victim sustained a minor laceration and was treated at the scene.
Investigators say the victims are all boys, ranging in age from 15 to 18 years old.
Pittsburgh Police spokeswoman Cara Cruz told reporters the incident stemmed from an altercation in a hallway and was not random.
In a statement, Pittsburgh Public Schools said the suspect used a small knife and stabbed three other students. Cruz confirmed one victim was transported to the hospital in critical condition, another in stable condition, and the third had minor injuries.
A male student was taken into custody at the scene after sustaining a hand laceration, according to Pittsburgh Public Safety. He was treated by medics and then transported to police headquarters for questioning.
Pittsburgh Public Schools announced the building is in "secure" status. It remains on lockdown while the scene is processed.
Classes are ongoing, but parents may pick up students if they choose, Cruz said.
Authorities urged anyone with video footage of the incident to contact Pittsburgh Police headquarters at 412-323-7800.
ABC News contributed to this report.