"She chose fraud over business failure. She chose to be dishonest," Assistant US Attorney Jeff Schenk said at the start of closing arguments. "That choice was not only callous, it was criminal."
Holmes, 37, is on trial in San Jose, California , in a case that has shed light on Theranos' failed endeavour to revolutionise lab testing with small machines that used only a few drops of blood.
Holmes' lawyer Kevin Downey told jurors at the start of his closing argument that the government's case was misleading and incomplete.
"The picture can change quite a good deal as a result of waiting for the full story," Downey said. He said prosecutors had not given them information about Theranos' successful projects with drug companies, which were included in Holmes' defence case.
Theranos was once valued at $US9 billion and vaulted Holmes to Silicon Valley fame. Wealthy private investors including media mogul Rupert Murdoch invested millions in the company after meeting with the founder, who was known for her Steve Jobs-like black turtleneck.
Schenk recapped testimony from more than two dozen witnesses, including patients who had received inaccurate results from Theranos tests for HIV and cancer.
He recalled testimony from six investors that Holmes gave them false impressions that Theranos devices could carry out a broad range of tests and that they were being used by the US military in the field.
Statements to investors and patients form the basis for nine counts of fraud.
Before finishing his argument, Schenk called on jurors to scrutinise Holmes' testimony, during which they saw encouraging emails telling her the company's technology worked.
Holmes had also received emails with negative information from employees, including on test accuracy. But investors only heard the positive information, he said.
"There's another word for that, and that's intent," he said.
Holmes conspired to commit those frauds with former Theranos chief operating officer Ramesh "Sunny" Balwani, Schenk said, with Holmes acting as the public face of Theranos and Balwani running its lab operations.
She also faces two counts of conspiracy.
The prosecutor told the jury that Holmes' testimony that Balwani was abusive towards her in their romantic relationship was a separate matter from the charges at issue.
Testifying in her own defence during the three-month trial, Holmes has said she did not intend to mislead anyone, and the company's laboratory directors were responsible for ensuring test accuracy.
Balwani, who is also charged with fraud and will stand trial separately, has pleaded not guilty.
Theranos collapsed after the Wall Street Journal published a series of articles starting in 2015 that suggested its devices were flawed and inaccurate. Holmes was indicted in 2018.