The governor of California, Arnold Schwarzenegger, has denied clemency to former Crips gang leader Stanley "Tookie" Williams.
Supporters of Williams have gathered outside the prison
Williams, 51, is now scheduled for execution at 0001 (0801GMT) on Tuesday.
On Monday evening, the US Supreme Court refused a stay of execution, as had California's Supreme Court and a federal appeals court.
A high-profile campaign with celebrity backing has fought to save Williams, who denies four murders in 1979.
With the rejection of his appeal by the US Supreme Court, Williams has exhausted all legal avenues.
He will be executed by lethal injection just after midnight local time at San Quentin prison, north of San Francisco.
Several hundred of his supporters have gathered at the prison gates to protest his innocence, burning candles, beating drums and singing.
The BBC's Peter Bowes says the atmosphere is growing increasingly tense, as the hour of Williams' execution approaches.
A handful of people are staging a counter demonstration in favour of the death penalty.
"After studying the evidence, searching the history, listening to the arguments and wrestling with the profound consequences, I could find no justification for granting clemency," Mr Schwarzenegger said.
The case has generated widespread debate in the US
"Stanley Williams insists he is innocent, and that he will not and should not apologise or otherwise atone for the murders of the four victims in this case. Without apology and atonement for these senseless and brutal killings, there can be no redemption," he said.
"Based on the cumulative weight of the evidence, there is no reason to second-guess the jury's decision of guilt or raise significant doubts or serious reservations about Williams' conviction and death sentence," the governor added.
Mr Schwarzenegger could have commuted the death sentence to life in prison without parole.
The California National Association for the Advancement of Colored People said it was saddened by the governor's decision.
"We believe this is a serious blow to our effort to fight gangs," its president, Alice Huffman, said.
During his 24 years in jail, Williams has won praise for his anti-gang books, earning Nobel Peace Prize nominations for his teachings.
His high-profile supporters have included Oscar-winning actor Jamie Foxx, rap star Snoop Dogg - himself a former Crips member- Bishop Desmond Tutu and the Reverend Jesse Jackson.
However, the relatives of some of his victims have insisted he did not deserve clemency because he had not owned up to his crimes and refused to inform on fellow gang members.