Carlos Ojeda, sought by the FBI and Drug Enforcement Administration in the US, was arrested on Thursday by agents from the CICPC anti-drugs squad in a commercial district in the east of Caracas, the Venezuelan interior and justice ministry said.
There were seven international arrest warrants issued for Ojeda, nicknamed "the Engineer" and suspected of co-ordinating much of the drug trafficking through Venezuela.
Venezuelan authorities are studying extradition requests for him, the ministry said.
Venezuela is a conduit for cocaine as it travels from neighbouring Colombia through the Caribbean to Europe and the United States. Traffickers use speedboats to ship drugs from its eastern coastline to boats or nearby islands.
Venezuela and US officials recently began working on a new co-operation deal to catch traffickers after Hugo Chavez, the Venezuelan president, severed ties with the DEA last year after accusing its agents of spying on his government.
Washington has branded the seven-year-old Chavez government a failure in the war on drugs.
Venezuela purged all 60 officers from the CICPC national investigative police drugs unit last month after accusations that its agents had mishandled or lost captured narcotics.