Ledell Lee, who was convicted of murdering his neighbour in 1993, was put to death just before midnight, with the clock ticking down on two impending deadlines.
Lee was pronounced dead at 11.56pm – 11 minutes after the three drug lethal injection cocktail began to pump into his veins.
The warrant for his execution was due to expire at midnight.
He was strapped to a gurney, and declined the opportunity to make a final statement before he died.
Arkansas had planned to stage eight executions within an 11-day period, because its stock of the sedative midazolam is due to pass its use-by date at the end of April.
But the first three executions were cancelled because of court rulings.
Hikma, the British manufacturers of the drug, have opposed its use in executions, and the makers of other drugs have tried to halt the executions in the courts, arguing that the prison authorities were unauthorised to use their products.
Midazolam has also been criticised for being ineffective in properly sedating prisoners so they feel no pain when two more drugs paralyse them, and then stop the heart.
But witnesses reported no apparent glitches or signs of suffering from Lee.
JR Davis, a spokesman for the Governor of Arkansas Asa Hutchinson, told reporters: “It is a sombre night all across Arkansas and that this is a responsibility he doesn’t take lightly and it’s one of the most grave things he’ll ever have to do.
“But in the end, we know the right thing was done tonight. And more importantly, justice for the first time since 1993 for Debra Reese’s family.”
Ms Reese was beaten to death 24 years ago, but lawyers for Lee said he maintained he was innocent and wanted a delay in execution to allow for fresh DNA testing.
Furonda Brasfield, from the Arkansas Coalition to Abolish the Death Penalty, said she was “dismayed that our governing officials wouldn’t allow the innocence claims to be fully explored”.
“We could have very well, executed an innocent man tonight, but we will never know that now,” she said.
By reactivating the death chamber, Arkansas has bucked a national trend which has seen a steady decline in the number of death sentences and of executions.
Last year the number of Americans executed fell to 20, compared to the 98 who were put to death in 1999.
Only five states carried out executions in 2016 and Arkansas is only the fourth state to carry out a death sentence this year.
Three more men are scheduled to die next week, while four others on Arkansas’ original list of eight have received temporary reprieves in the courts.
The difficulties of obtaining drugs, and legal challenges mean executions remain on hold in Oklahoma and Florida, which used to be among the most active death penalty states.
:: An update on death row inmate Richard Glossip can be heard in Ian Wood’s latest Dead Man Walking podcast.