A gunman sitting in a packed cinema stood up about 20 minutes into the film and began firing into the crowd, killing two and wounding at least nine others before fatally shooting himself.
The gunman initially tried escaping by blending into the fleeing crowd, but turned back when he saw police heading inside from the car park, authorities said.
Officers tailing him back into the cinema in the city of Lafayette, Louisiana, then heard a single gunshot and found him dead inside, police said.
They described the gunman as a 58-year-old “lone white male” with a criminal history but did not immediately disclose his name.
Lafayette police chief Jim Craft said the gunman was by himself and started the rampage by shooting the two people sitting in front of him.
At least one cinema-goer described the attack, saying an older man stood up about 20 minutes into the 7.10pm showing of the popular comedy Trainwreck and began shooting.
“We heard a loud pop we thought was a firecracker,” Katie Domingue told The Advertiser, a local newspaper.
“He wasn’t saying anything. I didn’t hear anybody screaming either,” said Ms Domingue, who added that she heard about six shots before she and her fiancé ran to the nearest exit, leaving behind her shoes and purse.
Stories of heroism immediately began to emerge with presidential hopeful Louisiana governor Bobby Jindal, who travelled to the scene within hours of the shooting, telling reporters that a teacher who was in the cinema jumped in front of a second teacher, saving her life. The second teacher then managed to pull a fire alarm to alert other members of the audience, he said.
“Her friend literally jumped over her and, by her account, actually saved her life,” Mr Jindal said.
President Barack Obama was briefed on the shooting aboard Air Force One, while on his way to Africa for a two-nation visit, the White House said.
In a BBC interview before the shooting, Mr Obama expressed frustration with 18 months left in office at his inability to take action on gun control. “If you look at the number of Americans killed since 9/11 by terrorism, it’s less than 100. If you look at the number that have been killed by gun violence, it’s in the tens of thousands,” Mr Obama said.
“And for us not to be able to resolve that issue is distressing.”
The shooting took place a week after the man who shot and killed 12 people at a cinema in Colorado in 2012, was convicted and on the very day a jury said his attack was cruel enough to consider sentencing him to death.
Nine people ranging in age from their late teens to their late 60s were wounded, Mr Craft said. At least one of those was in critical condition and being operated on at an area hospital, he said.
Mr Craft said at a news conference that police knew who the gunman was, and that he had a criminal history, but they were not immediately releasing his name.
Police said there were about 100 people inside the cinema at the time of the shooting.
Early yesterday, about a dozen law enforcement personnel were gathered at a motel in Lafayette to investigate whether the shooter had stayed there, officials said.
Police believe the gunman fired shots only at the cinema and had not waged an attack anywhere else beforehand.