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?"
John Grisham and Mahmoud Ahmadinejad Speak Out for Lewis
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.
The case also received unlikely attention from the president of Iran, Mahmoud Ahmadinejad. According to Iranian television, and first reported by The Associated Press, Ahmadinejad told a group of Islamic clerics in New York earlier this week that the Western media devoted "millions of Internet pages" to Sakineh Mohammadi Ashtiani, an Iranian woman who was sentenced to stoning for adultery, but that "nobody objects to the case of an American woman who is going to be executed."
Ahmadinejad's comments enraged even the most fervent foes of the death penalty.
"While it is long past time for the United States to join the majority of nations in the world and end the death penalty," said Elisabeth Semel, the director of the Death Penalty Clinic at the University of California at Berkeley, "the crime for which Ms. Ashtinani was convicted and sentenced to death, namely, adultery, would under no circumstances be a death eligible crime in the U.S., much less one that would be prosecuted in the first instance."
According to court papers, the trial judge that heard Lewis' case said that her sentence was made more difficult by the fact that she had pleaded guilty to her crimes and led the police to the triggermen. But he found that she had engaged in the "cold blooded, pitiless slaying of two men, horrible and inhumane." And that she had done it for profit, searching her husband's wallet for money as he lay dying.
Teresa Lewis' Final Night Before Execution
Before dying, Lewis was to have been allowed one "contact" visit with a family member and could choose to have clergy or spiritual advisers with her up to the time of execution. She was to be injected with three chemicals, thiopental sodium to render her unconscious, pancuronium bromide to stop her breathing and potassium chloride to stop her heart.
ABC News' Jim Sciutto contributed to this report.