After the final verdict, Zaw Lin and Win Zaw Tun were escorted back to prison.
Their battered bodies were found on a beach on the morning of September 15, 2014.
"I respect the verdict delivered by Thailand's Supreme Court in the Koh Tao murder case today", tweeted migrant workers' rights activist Andy Hall, who served as the global affairs advisor to the legal defence team.
The highest court ruled that all the evidence, including DNA samples and witness statements, proved their guilt.
The men displayed no emotion as they listened intently to a translator while the verdict was read at a court in the province of Nonthaburi, just north of Bangkok, the capital.
Lawyers for the two convicted men had claimed the evidence in the case was mishandled and that they made confessions under duress which they later retracted leading to questions about police competence and the judicial system in Thailand.
Police said Witheridge, 23, had been raped and bludgeoned to death and Miller, 24, had suffered blows to his head.
The Thai lawyer for the defendants contended they were provided with inadequate translators when talking to police, in addition to being physically abused into making confessions.
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The expert also alleged police failed to properly control the crime scene and mishandled the DNA evidence.
The trial was also plagued by accusations of human rights abuses and in 2016 global legal and forensic scientists said a DNA investigation by Thai Police Forensics Laboratory was incompetent with no evidence.
In 2015, the two men - both 22 - were found guilty of murder and sentenced to death.
A series of deaths there of other foreign tourists continue to contribute to unease about the case. Both defendants were also found guilty of rape, along with illegally entering and residing in Thailand, and Wai Phyo was also convicted of stealing Miller's phone and sunglasses. An appeals court upheld the guilty verdict in 2017.
In June a year ago Thailand lifted a de facto moratorium on the use of the death penalty, executing a man by lethal injection in the country's first execution since August 2009, rights groups said.
The case was also watched closely in Myanmar, where many felt they had been given an unfair trial.
A pro-bono legal team defending the men has said evidence collected by police was substandard.
"I consider that the death penalty sentence and conviction of the two accused Myanmar nationals, Zaw Lin and Wai Phyo, should instead have been reversed and quashed by the Supreme Court", Hall said.