Witnesses at the Century 16 cinema have told of a figure in a gas mask "slowly making his way up the stairs and firing, picking random people".
Police swamped the scene in the suburb of Aurora, in Denver, Colorado. Local hospitals were put on alert to prepare for the "mass casualty incident".
Media reports said 10 people died at the scene and four died later in hospital. The suspect, who is thought to have set off a smoke or tear gas bomb during the attack, was arrested a short time after the shooting.
A witness who was in the cinema at the time said: "We heard anywhere from 10 to 20 shots and little explosions going on.
"Shortly after that we heard people screaming. Then they came on PA system and said everyone needed to get out.
"As soon as we got out, there were people running around and screaming."
Another witness said the gunman, who is thought to be in his mid 20s, opened fire during a shoot-out scene in the movie, The Dark Knight Rises. He said the theatre was filled with thick smoke.
Local radio reporter Brenda Stuart said movie-goers at first thought the attack was part of the film.
She told Sky News: "A lot of people thought the gunshots were part of the movie. Then bullets started flying."
While initial reports had suggested a second gunman was involved, Aurora Police Chief Dan Oates said there was no immediate evidence of this. Police have confirmed the number dead in the shooting, with spokeswoman Cassidee Carlson saying: "The scene is still very active."
Nicole Williams, for Denver's Swedish Medical Center, said three people had been admitted to that hospital with gunshot wounds and were in critical condition.
She said emergency crews told her staff to prepare for several more patients from the shooting scene. Ms Williams said she was told that "somebody opened fire with some sort of weapon during the Dark Knight movie. Ms Stuart added: "Police officers are taking people to hospital themselves, not waiting for ambulances."
Another hospital, Denver Health, had received six wounded, one of whom was in a critical condition. Emergency workers say there could be several more patients.Dozens of police were at the scene, and the authorities evacuated the area while they checked if there was an explosive device at the complex.
Witness Hayden Miller told KUSA-TV that he was inside Theatre 16 and heard several shots.
"Like little explosions going on and shortly after that we heard people screaming," he told the station.
Hayden said at first he thought it was part of a louder movie next door. But then he saw "people hunched over leaving theatre".
Local TV pictures showed police cars surrounding the shopping mall where the Century 16 cinema is located.
Colorado has a sad and bloody association with mass shootings after it was made infamous by the Columbine High School massacre in 1999 just a 30 minute drive away.
Two senior students, Eric Harris and Dylan Klebold, embarked on a shooting spree in which a total of 12 students and one teacher were murdered.
The state's gun laws have been under regular scrutiny since the events of Columbine.
It is still legal to carry a firearm in a vehicle, loaded or unloaded, if its use is for "lawful protection."
And it is possible to apply for a permit from the Sheriff's department to carry a concealed weapon.