Media reports said five or six people had been killed in the incident and a gunman reportedly shot dead by police. Police did not confirm the number of fatalities.
Devon & Cornwall Police said they were called to the Keyham area of the city at 6.10 p.m. on Thursday.
"There have been a number of fatalities at the scene and several other casualties are receiving treatment," they said.
Local lawmaker Johnny Mercer said on Twitter: "The incident is not terror related, and neither is the suspect on the run in Plymouth".
South Western Ambulance Service earlier said it had responded to the incident with a significant number of resources, including Hazardous Area Response Teams (HART), multiple ambulances, air ambulances, multiple doctors and senior paramedics.
