Lewis, 41, died by injection at 9:13 p.m. at the Greensville Correctional Center in Jarratt, Va., according to The Associated Press. As supporters of her victims looked on, the fatal dose was administered.
Lewis' final words were a message for the daughter of the husband she had killed.
"I just want Cathy to know that I love her, and I'm very sorry," she said.
A circuit court judge determined that Lewis was the "mastermind" of a grisly plan to hire two hit men to kill her husband and stepson in 2002. Lewis stood by while Julian Lewis and son Charles Lewis were shot at close range.
Teresa Lewis pleaded guilty to her role in the crime and repeatedly expressed regret. But while the triggermen received sentences of life in prison, Lewis was sentenced to death.
The U.S. Supreme Court refused to hear her appeal earlier this week, and Virginia Gov. Bob McDonnell has denied her petitions for clemency.
Lewis, case number 09-4, became the 12th woman put to death in the United States since 1976, and left behind 60 women remaining on death row nationally, who constitute less than 2 percent of the total death row population. She joined a group of about 40 women who have been executed in the United States in the past 100 years, according to the Death Penalty Information Center, a group that opposes the death penalty and tracks its impact.
Those opposed to Lewis' death sentence said the fact that she was a woman should not allow her to be treated differently. What they found troublesome was that Lewis had been diagnosed as borderline mentally retarded and received a more severe sentence than those who pulled the trigger.
"It would be grossly unfair if the one person among those involved who is probably the least danger to society, who is certainly no more guilty than those who carried out the murders and whose disabilities call out for mercy, is the only person scheduled to die for this crime," said Richard Dieter, the executive director of the Death Penalty Information Center.
John Grisham, the well-known crime novelist, agreed.
"Why," he wrote in an op-ed article for The Washington Post, "did the triggermen get life without parole while Lewis received a sentence of death? Ostensibly, it is because she was the ringleader and thus more culpable. But what could make a killer more culpable than repeatedly shooting a sleeping victim?"
Grisham believed that Lewis' death sentence had little to do with fairness.
"Like other death sentences," he said, "it depended more upon the assignment of judge and prosecutor, the location of the crime, the quality of the defense counsel, the speed with which a co-defendant struck a deal, the quality of each side's experts and other such factors."
Lewis' supporters created a website called "Save Teresa Lewis" and posted a haunting recording of her singing a biblical hymn, "I Need a Miracle," on YouTube. While they didn't argue that Lewis was innocent, they did not believe she should be put to death.