Authorities didn't identify the suspect or victims but said two were male and one was female.
The suspect wasn't believed to be a student, but it appeared there was a relationship between the suspect and victims killed, Police Chief Chris Walsh said.
"We're locating next of kin, and working on notification absolutely as fast as we can," he said.
Walsh said he wanted the community to know there was no further threat.
"I want to emphasize that this is a horrible tragedy," Walsh said. "And I want the city to, well I can't say, you know just feel safe right now. There is no one at large."
The attack occurred just before 9 a.m. Friday at the two-year community college in Casper, about 250 miles northwest of Denver.
Class was in session and the campus was locked down after the attack and the science building was evacuated, but the lockdown had ended by early afternoon.
Police provided some details in a news conference streamed live by the Casper Star-Tribune.
Political science instructor Chris Henrichsen said he was showing the film "Frost/Nixon" to his Wyoming and U.S. government class when he stepped into the hall to get something for a student and was told a homicide had occurred on campus.
He went back to his classroom, where students were getting messages about the campus lockdown on their phones.
"We locked the door and waited for further instruction," Henrichsen said.
The class finished watching the remaining 10 minutes of the movie and remained locked down 20 minutes after that, he said.
The students then were sent home, but some who parked near a different campus building where the attack occurred had to leave their cars there, Henrichsen said.
Henrichsen said he saw nothing unusual or suspicious on campus before the attack.
Walsh said 33 law enforcement officers from different agencies responded to the college after receiving reports about an attack. He said authorities first thought it might have been an "active shooter type situation."
"We quickly contained the building, and started a sweep through the building," he said.
Walsh said within minutes of the initial call, there was another report of a traumatic injury about two miles southwest of campus. He would not specify where the suspect was found dead, but said, "one of those who is deceased is who we believe was committing all the violence."
Casper is Wyoming's second-largest city with a population of about 56,000. Wyoming residents refer to it as the "Oil City" because it's a hub for the state's small oil industry.
Casper is flanked to the south by Casper Mountain, scene of a massive wildfire in September that burned more than 24 square miles of forest and meadows and destroyed 37 homes and cabins.