Knighton, a 200 metres world silver medallist in 2023, was charged with an ADRV in May 2024 when a doping test revealed the presence of Epitrenbolone, an anabolic steroid on WADA's prohibited list.
Although a tribunal had cleared him of wrongdoing after he blamed meat contamination in an oxtail dish, World Athletics and the global anti-doping body appealed to sport's highest court, which upheld their appeals.
The ban prevented the 21-year-old from competing at the World Athletics Championships, which got underway in Tokyo on Saturday, while it will also see him miss the Los Angeles Olympic Games in 2028.
"This case was based on probability. USADA independently sourced and tested oxtail from the same restaurant where Erriyon ate, and the testing proved that the meat that was purchased there had traces of trenbolone," his agent John Regis told Reuters.
"This should have been an open and shut case - to pretend that it is a coincidence is a farce. There is no question that the meat that Erriyon ate was contaminated with the very substance he tested positive for.
"It is indisputable that American meat can be contaminated with steroids, because steroids are (used) by the beef industry to increase their profits - not for health or safety reasons."
Knighton had argued that the ADRV was caused by the ingestion of an oxtail dish contaminated with trenbolone, a known livestock growth promoter used legally in beef cattle produced in and exported to the United States.
Regis argued that Knighton provided stronger evidence of food contamination than any athlete before him, yet WADA still chose to appeal his case, comparing it to the Chinese swimmers who were cleared without charges or arbitration.
He also suggested WADA's actions were politically motivated, driven by hostility toward USADA rather than based on the merits of the case.
"We stand with our client Erriyon Knighton and believe he did not deliberately dope, but he is an athlete who has been found guilty of choosing the wrong restaurant to eat food," Regis added. "This case is not over."
However, WADA were firm in their view that Knighton had failed to establish meat contamination as the source.
"During its appeal to CAS, WADA brought forward several experts, including some who had given evidence for USADA in the first instance proceedings," WADA said.
"(They) were able to demonstrate to the CAS Panel that meat contamination was not a plausible explanation for how the prohibited substance was found to be in the athlete's system."