The Court of Arbitration for Sport (Cas) has banned Alberto Contador for two years for doping.
He has been stripped of his 2010 Tour de France victory and, with his suspension running until 6 August this year, will miss the 2012 Tour.
The Spaniard, 29, was found guilty of doping after testing positive for clenbuterol during the 2010 Tour.
He has maintained that the failed test resulted from eating contaminated meat.
Andy Schleck of Luxembourg, who finished second to Contador in the 2010 Tour de France, is set to be elevated to champion.
Under the rules of the world governing body, Union Cycliste Internationale (UCI), Contador also forfeits all his wins in 2011, which include the Giro d'Italia. Italian Michele Scarponi will take that title.
The ban is backdated and, as such, Contador can resume competition on 6 August, 2012 - two years after he was informed of his failed test.
UCI president Pat McQuaid said: "This is a sad day for our sport. Some may think of it as a victory, but that is not at all the case.
"There are no winners when it comes to the issue of doping: every case, irrespective of its characteristics, is always a case too many."
Contador was initially cleared in February 2011 by the Spanish cycling federation (RFEC).
The UCI and World Anti-Doping Agency (Wada) appealed against that decision to Cas, which upheld the appeal after twice postponing the hearing.
The verdict was handed down by a three-man jury consisting of Israeli Efraim Barack, Quentin Byrne-Sutton of Switzerland and German Ulrich Haas.
Wada regards clenbuterol - a fat-burning and muscle-building supplement - as a zero-tolerance drug.
Contador is one of only five cyclists to win the three Grand Tours - the Tour de France, the Giro and the Spanish Vuelta.
A winner of the Tour in 2007 and 2009, he becomes only the second cyclist to lose his title for doping, after American Floyd Landis tested positive for testosterone in 2006.
