Fabio Ochoa was arrested in a joint US-Colombian effort
He was handed over to officials of the US Drug Enforcement Agency at Bogota airport, where an aircraft took off for the US.
He denies charges of involvement in smuggling cocaine.
He turned himself in to Colombian authorities in the early 1990s under a deal which meant he would plead guilty to some minor drugs smuggling charges and not be extradited to the US.
He was required to stay away from the drugs trade, but according to the BBC's Bogota correspondent the lure proved too strong.
US victory
Mr Ochoa's handover is a victory for US officials who have long sought the extradition of Colombian drug lords who are flooding the US with cocaine and heroin.
The move comes four days before US Secretary of State Colin Powell is to visit Bogota for a meeting with President Andres Pastrana to discuss anti-drugs efforts.
Mr Pastrana signed Mr Ochoa's extradition papers last month.
Mr Ochoa was one of the most prominent figures arrested in Operation Millennium, a joint Colombian-US assault on the drugs trade.
He faces a federal indictment from Fort Lauderdale, Florida, which alleges that he was part of a gang that exported 30 tonnes of cocaine a month to the US.
The extradition had been suspended on 31 August by Judge Claudia Merchan, but on Friday she reversed that decision.
In Medellin Mr Ochoa's sister Martha Nieves Ochoa protested his innocence saying: "Justice did not triumph, and all Colombians have lost."
Mexican cartel bust
Meanwhile, the authorities in Mexico say six leaders of one of the country's main drug syndicates have been arrested, dealing a major blow to the cartel.
The Attorney General, Rafael Macedo, said among those arrested was Arturo Guzman, who is alleged to have run the Sinaloa drug cartel for seven years.
The group smuggled Colombian cocaine through Mexico into the United States.
The authorities hope his capture will lead them to his brother, Joaquin Guzman - the most senior figure in the cartel - who escaped from a high security prison earlier this year.
The American Drug Enforcement Agency wants the Guzman brothers for allegedly building a tunnel across the Mexico-US border to smuggle tonnes of cocaine.