Holmes is accused of killing 12 people and wounding dozens more in an Aurora movie theater.
He will wear the harness, which will be anchored to the floor, because of the violent nature of his alleged crimes, a judge said.
Judge Carlos Samour Jr. will send out 5,000 jury summons and expects at least 3,200 people will end up in court, he ruled on Thursday.
That would mean each of the 450,000 Arapahoe County residents eligible for jury duty would have a 1 in 90 chance of being called, for this one case alone, court spokesman Rob McCallum told CNN.
The idea is to bring in 800 prospective jurors at a time on Thursdays and Fridays early next year, a process that McCallum says could take three to four weeks.
Those thousands will be winnowed down to 12 men and women for the start of the trial, which is set to begin February 3. It is expected to last four months.
Asking more people than usual to come to court for high-profile cases is common in the U.S. justice system, given concerns many of them already know the story and have strong opinions about it.
In Florida, for example, there was a 500-person jury pool for the now-ongoing murder trial of George Zimmerman, who is accused in the killing of teenager Trayvon Martin -- a case that drew national headlines for weeks.
So too, of course, did what happened just after midnight the night of July 20, 2012, in the Denver suburb of Aurora.
It was then and there, authorities say, that a man walked through an exit door into a crowded Theater 9 of the Century movie complex as a late-night premiere of the Batman sequel "The Dark Knight Rises" played.
The former neuroscience graduate student wore all-black, a ballistic helmet, a tactical ballistic vest, protective leggings, a throat and groin protector, and a gas mask, police say. And he carried an arsenal that included two Glock handguns, an AR-15 rifle, a shotgun and 6,295 rounds of ammunition, Bureau of Alcohol, Tobacco, Firearms and Explosives agent Steve Beggs has testified.
"He didn't care who he killed," prosecutor Karen Pearson told a judge during a preliminary court hearing in January, adding Holmes chose his venue carefully to cage his victims. "He intended to kill them all."
After the carnage and Holmes' subsequent capture outside the theater, he was charged with 166 counts of murder, attempted murder and weapons violations.
Since his arrest, much of the in-court discussion has resolved around Holmes' mental state.
Judge Samour earlier this month accepted the defense's plea of not guilty by reason of insanity. He was then taken to the Colorado Mental Health Institute in Pueblo for evaluation, and is expected to be back in Arapahoe County Jail on August 2.
Prosecutors in Arapahoe County announced in April they would seek the death penalty.
Despite the notoriety of the mass shooting, the judge ruled Thursday that the empaneled jury will not be sequestered, as Holmes' defense team requested. Making it so they couldn't go home throughout the prolonged trial, Samour said, was an "unnecessarily drastic, expensive and impractical remedy that ... will create an extreme and undue hardship for jurors."
The judge also ruled against the defense's attempt to prevent jurors from using phones or computers, barring their use in court but saying preventing them from using them outside is "unreasonable and unfair."
One thing jurors won't be able to see is restraints on Holmes.
As someone accused of "multiple violent crimes," Samour says that Holmes must be restrained carefully during his trial.
But the judge said he needn't wear handcuffs or shackles. Instead, the judge ruled, Holmes will "wear a harness under his clothing which will not be visible to the jury" and will be anchored to the floor.
CNN's Carma Hassan contributed to this report.