US District Judge Sim Lake on Monday completed the task of selecting and swearing in the jurors - eight women and four men - and extensively warned them not to talk to friends and family about the case, and warned that media reports are not evidence.
Both Lay, 63, and Skilling, 52, together face 38 charges of fraud and conspiracy, relating to their roles in the scandal. They deny all charges.
Enron's collapse in 2001 left it in a $US31 billion debt and 4,000 workers without jobs. It also wiped out billions of dollars in workers' retirement accounts.
Judge Sim Lake turned down a defence request to question potential jurors, saying he would conduct the vetting process himself. The trial could start on Wednesday.
The court came to order on Monday with ex-Enron executives Lay and Skilling sitting at separate tables in full view of 100 prospective jurors from 14 area counties.
The judge began by welcoming the would-be jurors and thanking them for their patience after their early morning arrival, which involved using a back entrance to avoid nearly two dozen TV cameras and other journalists gathered at the main entrance to the downtown federal courthouse.
"We have some of the finest lawyers in the United States trying this case," Lake said. While assuring prospective jurors that this trial will be one of the most interesting cases they could see, he also informed them that it could last four months.
Both Lay and Skilling looked relaxed and ready for jurors in the biggest corporate scandal in recent years in US.
"We're looking forward to it. We're ready," said Daniel Petrocelli, Skilling's lead trial lawyer about the trial. Skilling declined comment, as did Lay, who simply said
"Fine, how are you?" when a reporter asked how he felt.
If found guilty in Enron's hometown, both could face long prison sentences for their alleged parts in one of the most damaging scandals to hit corporate America.
Lay entered the courthouse along with his wife Linda and accompanied by his defence team. Skilling followed a few moments later with his lawyer, Daniel Petrocelli.
Asked by reporters if this was a chance to clear his name, Lay replied, "It certainly is." Lay also said he was "looking forward" to getting his day in court. Before prosecutors and attorneys began picking the jury, one former federal prosecutor said the term "jury selection" is a misnomer.
"It's really jury elimination," said Southern Methodist University law professor and one-time Justice Department lawyer Linda Eads.
Early in the process, at least one would-be juror told Lake he didn't think he was up to the task of deciding the fates of Skilling and Lay. That individual told the judge his grandmother taught him: "Judge not lest ye be judged," a sentiment also shared by those he worships with at church.
"Everybody in here at least at one point in time has been falsely accused of something,'' he told Lake, who reminded those in his courtroom that this case is about law, not morality.