The Court of Arbitration for Sport (CAS) in Lausanne dismissed the appeal filed by the Russian Paralympic Committee, which sought to overturn the August 7th ban by the International Paralympic Committee (IPC).
The IPC took the tough action after the release of a bombshell report commissioned by the World Anti-Doping Agency (WADA), detailing drug-cheating directed by government officials and affecting dozens of sports.
Citing evidence compiled by WADA lead investigator Richard McLaren, the IPC argued that Russia's disabled athletes had failed to comply with global anti-doping codes.
The CAS said Russia in its appeal “did not file any evidence contradicting the facts on which the IPC decision was based.”
In a statement, the court “confirmed” Russia's ban from the Rio Paralympics, which run from September 7th to 18th.
Russian officials had voiced confidence of a victory at CAS and immediately took issue with Tuesday's ruling.
Sports minister Vitaly Mutko, a central figure in the McLaren report, blasted the CAS decision as “more political than legal.”
“The decision is not in the legal domain,” TASS news agency quoted Mutko as saying. “There was no reason for rejection but it happened.”
However IPC President Philip Craven said the decision “underlines our strong belief that doping has absolutely no place in Paralympic sport, and further improves our ability to ensure fair competition and a level playing field for all Para athletes around the world.”
The decision was applauded by the president of Germany's National Paralympic Committee, Friedhelm Julius Beucher.
“The judgement is a sign of consistent zero-tolerance on doping,” he said.
“Exclusions are always tragic, but there are rules in sport and anyone who doesn't follow them gets shown a red card,” he added.
The Paralympics ban was the latest blow to Russian sport, which has been condemned by a mountain of doping allegations in recent months.
The country narrowly escaped an outright International Olympic Committee ban from the just-concluded Rio Games, but still saw dozens of its athletes barred, including the entire track and field team.
Russia continues to deny the findings of the McLaren report, including the involvement of the sports ministry and the Russian secret service in doping fraud at the 2014 Sochi Winter Olympics.
Russian Paralympic Committee president Vladimir Lukin had sought to portray his athletes as independent from the Moscow government.
But the IPC said it did not believe that disabled Olympic hopefuls were untouched by the pervasive cheating in the country.
Craven said previously that Russia's “thirst for glory at all costs has severely damaged the integrity and image of all sport”.
“Their medals over morals attitude disgusts me.”
The Paralympics, held every four years for athletes with disabilities, has taken place in various forms since 1948 but has grown in importance over the past 20 years.
An estimated 250 Russian competitors had been slated to take part in Rio and many had continued training ahead of the CAS decision.
That included 19-year-old backstroke specialist Alexander Makarov, who suffers from arthrogryposis, a congenital condition that limits the limbs' movements.
He told AFP last week that he was trying “not to think” about being barred from Rio, as he churned through 50 laps during a morning training session outside Moscow.
Nearly 4,300 athletes from 164 countries took part in the 2012 London Paralympic Games.
The 2016 Rio Paralympics will see athletes compete in 23 disciplines over 11 days.