Lay blamed the implosion of Enron, once the seventh-largest US company, on a series of devastating circumstances that included theft by the chief financial officer, negative press, a bear market and investor anxiety after the September 11, 2001, attacks.
"I don't think there ever was a conspiracy of any kind," he said.
His testimony, defending against criminal fraud and conspiracy charges that could send him to prison for the rest of his life, represented an extraordinary moment in an era in which Lay and Enron, fairly or not, have come to be seen as symbols of corporate scandal.
Lay, 64, a former chairman and chief executive of the company, said he was eager to tell the truth about what happened at Enron, a story he said was distorted by overzealous federal investigators and bad publicity.
Under questioning from a defence lawyer, he made a point of accepting "full responsibility for everything that happened at Enron" and acknowledged the thousands of jobs and billions of investor dollars that were vaporised in its collapse.
"I'm sure there's absolutely nothing in my life, including the loss of life of many of my loved ones, that even comes close to the same level of pain, and the same enduring pain, that it has caused," he said.
Lay explicitly denied committing fraud, participating in a criminal conspiracy or knowingly misleading investors and employees about the health of the company.
He spoke in conversational and even folksy terms, appearing more relaxed than his co-defendant, former Enron CEO Jeffrey Skilling, who testified earlier this month and played the brilliant strategist to Lay's affable visionary.
He even cracked a few jokes, some at the expense of lawyers.
Skilling (L), a former Enron CEO,
testified earlier this month
When his lawyer George Secrest asked him what his birth date was, he deadpanned: "I appreciate the fact that you do acknowledge I was born."
The jokes appeared to fall flat with jurors.
When Secrest asked Lay what his worst mistake was as head of Enron, Lay said the answer was easy - hiring Andrew Fastow, who has admitted to stealing tens of millions of dollars from the company.
"It all began with the deceit of Andy Fastow," Lay said of the former CFO.
Fastow was a pivotal piece of the government's case against Lay and Skilling, insisting both men knew the company was in poor health in 2001 even as they were making public statements to the contrary.
Fastow has agreed to serve 10 years in prison after pleading guilty to two counts of conspiracy.
In Lay's version of events, Fastow's theft was the beginning of the end for Enron. Lay also blamed short sellers, who were in effect betting on Enron's failure, and a series of negative stories in The Wall Street Journal in late 2001.
Set against an economy already reeling from the bursting of the technology-stock bubble in the late 1990s and the 2001 terror attacks, Enron was faced with "a firestorm that we couldn't stop", Lay told jurors.
Lay compared that firestorm to a classic run on the bank, with investors and creditors pulling out cash. He maintained the company was fundamentally sound as late as six weeks before it entered bankruptcy protection in December 2001.
"I'm sure there's absolutely nothing in my life, including the loss of life of many of my loved ones, that even comes close to the same level of pain, and the same enduring pain, that [Enron's collaps] has caused"
Lay also directly contested Fastow's claim that the CFO had given him a rundown in 2001 of huge, looming write-offs, a massive accounting error and deterioration of fragile financial structures Enron allegedly used to mask losses.
Asked whether Fastow ever discussed such a list of impending problems with him, Lay said: "That did not happen, period."
Outside court, Lay said he was pleased to begin addressing "a lot of the lies about me, about Mr Skilling and about Enron. And we're going to keep doing that".
Lay's testimony, expected to last at least through Wednesday, follows two weeks in which Skilling declared his own innocence on the witness stand. Skilling's testimony included some prickly exchanges with a prosecutor on cross-examination.
Character witnesses and expert witnesses are expected to follow Lay, and the defence could wrap up by the end of next week.
The government will have the chance to present a rebuttal case before jurors hear closing arguments and begin deliberating.