No motive has emerged in nearly 10 months of hearings, but Holmes' attorneys have repeatedly said their client is mentally ill. He was being treated by a psychiatrist before the attack.
The insanity plea carries risks for both sides. Holmes will have to submit to a mental evaluation by state-employed doctors, and prosecutors could use the findings against him.
"It's literally a life-and-death situation with the government seeking to execute him and the government, the same government, evaluating him with regard to whether he was sane or insane at the time he was in that movie theater," said attorney Dan Recht, a past president of the Colorado Criminal Defense Bar.
Among the risks for prosecutors: They must convince jurors beyond a reasonable doubt that Holmes was sane. If they don't, state law requires the jury to find him not guilty by reason of insanity.
"That's a significant burden on the prosecution," Recht said.
If acquitted, Holmes would be committed to the state mental hospital indefinitely.
A judge entered a standard not guilty plea on Holmes' behalf in March, and he needs court permission to change it. Recht said it's a foregone conclusion the judge will accept the new plea to preclude appeals later.
The mental evaluation could take weeks or months. Evaluators will interview Holmes, his friends and family, and if Holmes permits it, they'll also speak with mental health professionals who treated him in the past, said Dr. Howard Zonana, a professor of psychiatry and adjunct professor of law at Yale University.
Evaluators may give Holmes standardized personality tests and compare his results to those of people with documented mental illness. They will also look for any physical brain problems.
Zonana estimates he has conducted around 200 mental evaluations of criminal defendants, including some death penalty cases.