Police say suspect, who remains at large, targeted businesses in Lewiston including a bar and bowling alley.
Two law enforcement officials in the city of Lewiston told The Associated Press news agency on condition of anonymity that the death toll from the attack was likely to rise.
US media outlet NBC News, citing an unnamed Lewiston law enforcement official, said at least 22 people had been killed and as many as 60 wounded in the attack.
State and local police previously reported there had been an active gunman on Wednesday night and that they were searching for a suspect who remained at large.
They did not say how many people had been killed or hurt.
“There is an active shooter in Lewiston,” Maine state police said on the social media platform X. “We ask people to shelter in place. Please stay inside your home with the doors locked. Law enforcement is currently investigating at multiple locations.”
The gunman targeted a bar, a bowling alley and a Walmart distribution centre, according to the local Sun Journal newspaper.
On its website, Central Maine Medical Center said staff were “reacting to a mass casualty, mass shooter event” and were coordinating with area hospitals to take in patients.
The Androscoggin County Sheriff’s Office released two photos of the suspect on its Facebook page that showed a bearded man in a long-sleeved shirt and jeans with a rifle raised to his shoulder.
Maine State Police were planning to hold a news conference on the attack later on Wednesday night.
Angus King, an independent senator for Maine who is currently in Washington, DC, said he was “deeply sad for the city of Lewiston and all those worried about their family, friends and neighbours” and was monitoring the situation.