The gunman remained at large at the Clackamas Town Center near the Portland suburb of Happy Valley, said Steve Campbell, spokesman for the city.
"There is an active shooter at the Clackamas Town Center," Campbell said.
The Oregonian newspaper reported on its website that two people had been killed by a man using a semi-automatic rifle who may have also been wearing body armor. The paper said the shooting occurred near the mall's food court.
"The scene outside as I was leaving was just chaos," witness Isabel Valentine told the paper. "Police were everywhere, people were crying and screaming, and we still don't know exactly why this all happened."
Oregonian sports reporter John Canzano, who said he was at the mall when the shooting began, tweeted that "panicked people are running from the mall" and later urged his followers simply to "pray."
Police and SWAT teams established a perimeter around the scene and worked to evacuate the mall as they searched for the shooting suspect. The Clackamas County Sheriff's office urged members of the public to avoid the area.
A spokeswoman for the mall said she had no immediate information and directed calls to law enforcement.
(Reporting by Teresa Carson, Dan Whitcomb and Alex Dobuzinskis; Writing by Dan Whitcomb; Editing by Cynthia Johnston and Peter Cooney)