The US has carried out its 1,000th execution since capital punishment was reintroduced in 1976.
Boyd had never denied his guilt
Kenneth Boyd, a convicted killer, was put to death by lethal injection in North Carolina for the murder of his estranged wife and her father in 1988.
He was given three drugs - one to put him to sleep, another to paralyse him, and a third to stop his heart.
Though a majority of people in the US back the death penalty, polls indicate support is starting to wane.
"This 1,000th execution is a milestone. It's a milestone we should all be ashamed of," Boyd's lawyer Thomas Maher said after watching the execution.
Amnesty International's Kate Allen said that the landmark death "puts the US in the same company as countries like China, Iran, Saudi Arabia and Vietnam".
Boyd, 57, was pronounced dead at 0215 (0715 GMT), state Department of Correction spokeswoman Pam Walker said.
He had spent his last hours with visiting friends and family, including one of his sons, 35-year-old Kenneth Smith and his wife Kathy and two children.
There were protests outside the prison in Raleigh
It was to Kathy Smith that Boyd addressed his last words saying:
"Look after my son and my grandchildren. God bless everybody in here."
A group of about 150 death penalty opponents had gathered outside the Central Prison in Raleigh, North Carolina where the execution took place. Sixteen were reportedly arrested when they tried to enter the facility.
Any hope of a reprieve ended when the Supreme Court rejected Boyd's final appeal and the North Carolina Governor, Mike Easley, said he could find "no compelling reason to grant clemency".
"Tonight justice has been served," Sheriff Sam Page said outside the prison.
Boyd spent 11 years on death row after being convicted of stalking and shooting his estranged wife, Julie, and her father, Thomas.
US EXECUTIONS SINCE 1976
Texas - 355
Virginia - 94
Oklahoma - 79
Missouri - 66
Florida - 60
Georgia - 39
North Carolina - 38
South Carolina, Alabama - 34 each
Louisiana, Arkansas - 27 each
Arizona - 22
Ohio - 19
Indiana - 16
Delaware - 14
Illinois - 12
Nevada, California - 11 each
Mississippi, Utah - 6 each
Maryland, Washington - 4 each
Nebraska, Pennsylvania - 3 each
Kentucky, Montana, Oregon - 2 each
Colorado, Connecticut, Idaho, New Mexico, Tennessee, Wyoming - 1 each
US government - 3
Source: US Death Penalty Information Center
One of the couple's sons was pinned under his mother's body as she died. Another son grabbed the gun.
Boyd never denied his guilt, though he has claimed that his experiences in Vietnam contributed to his state of mind on the day of the killings.
Boyd said that the death penalty was "nothing but revenge".
Relatives of his victims said he deserved to die.
In a prison interview with the Associated Press this week, Boyd said he did not want to be connected to the 1000th execution tag: "I'd hate to be remembered as that," he said. "I don't like the idea of being picked as a number."
Capital punishment in the US was banned for 10 years, before the Supreme Court overturned the ban in 1976.
A year later, Gary Gilmore became the first to die - by firing squad in the state of Utah.
The BBC's Justin Webb in Washington says that in recent years, enthusiasm for the punishment has dwindled in the US.
Although a majority still approve of it, public support for the death penalty has dropped and the courts have been less inclined to use it.
US SUPPORT FOR DEATH PENALTY
Question asked: Are you in favour of the death penalty for a person convicted of murder?
All samples 800-1,000 adults
Face-to-face and telephone interviews
Margin for error +/- 3%