Thirteen minutes after a doctor administered a lethal injection at the state's death chamber in McAlester, Clayton Lockett lifted his head and started mumbling and the execution was halted, said state corrections department spokesman Jerry Massie.
Lockett died of an apparent heart attack about 40 minutes after the procedure started, he added.
"We believe that a vein was blown and the drugs weren't working as they were designed to. The director ordered a halt to the execution," Mr Massie said.
The troubled execution was expected to have national implications, as lawyers for Death Row inmates have argued that new lethal injection cocktails used in Oklahoma and other states could cause undue suffering and violate constitutional protections against cruel and unusual punishment.
"This could be a real turning point in the whole debate, as people get disgusted by this sort of thing," said Richard Dieter, executive director of the Death Penalty Information Centre, which monitors capital punishment.
"This might lead to a halt in executions until states can prove they can do it without problems. Someone was killed tonight by incompetence," Mr Dieter said.
Witness Ziva Branstetter said Lockett was thrashing about and appeared to be in pain. The state blocked off the scene from witnesses a few minutes after the troubles started, by drawing a curtain on the execution chamber.
"His body was sort of bucking. He was clenching his jaw. Several times he mumbled phrases that were largely unintelligible," she said.
The execution had been put on hold for several weeks due to a legal fight over a new cocktail of chemicals for the lethal injection, with lawyers arguing the state was withholding crucial information about the drugs to be used.
Last week, Oklahoma Supreme Court lifted stays of execution for Lockett and another inmate who was also scheduled to be executed on Tuesday, saying the state had provided enough information about the lethal injection cocktail to meet constitutional requirements.
The other inmate, Charles Warner, who was scheduled to be put to death two hours after Lockett, has now been granted a 14-day stay of execution.
"I have asked the Department of Corrections to conduct a full review of Oklahoma's execution procedures to determine what happened and why during this evening's execution of Clayton Derrell Lockett," Governor Mary Fallin said.
Oklahoma set up a new lethal injection procedure earlier this year as it was no longer able to obtain the drugs it had once used for executions. Oklahoma and other states have been scrambling to find new suppliers and chemical combinations after drug makers, mostly in Europe, imposed sales bans because they objected to having medications made for other purposes being used in lethal injections.
"After weeks of Oklahoma refusing to disclose basic information about the drugs for tonight's lethal injection procedures, tonight Clayton Lockett was tortured to death," said Madeline Cohen, an attorney for Warner.