Officers responded to the shooting at East High School at about 10 a.m., the Denver Police Department said in a social media post.
Two adult victims were located and taken to hospitals, and police said the suspect was no longer believed to be on scene.
East High School, not far from downtown near a busy street that cuts through the city, was placed on a lockdown as police investigated the shooting.
It was unclear if the shooting happened inside or outside the school. Denver Public School said the victims were faculty members.
Earlier this month students from the school skipped class and marched to Colorado’s state Capitol to demand stricter gun laws, following the death of a fellow student who was shot while sitting in a car near school.