Stories in the Wall Street Journal and New York Times outlined long-simmering accusations from the United States that the governments of President Nicolas Maduro and his predecessor Hugo Chavez have facilitated cocaine shipments.
But Cabello, said to be the highest-ranking target of the U.S. probes, called them baseless accusations that were part of a campaign to destabilize socialism in Venezuela.
"It would never occur to us to get involved in something that would hurt young people," the National Assembly head and No. 2 in the ruling Socialist Party told Venezuela's parliament.
"Those who today accuse me of trafficking should present one piece of proof, just one," he said. "This isn't a campaign against me, it's a campaign against the whole fatherland."
Socialist legislators chanted, "We're all Diosdado", and passed a motion lauding him as a "hero".
Citing more than 12 people familiar with the probes, the Wall Street Journal on Monday said federal prosecutors in New York and Miami and a Drug Enforcement Administration unit were gathering evidence from former traffickers, military defectors and people once close to top Venezuelan officials.
The paper defended its reporting on Tuesday after Cabello's comments.
"We stand by our story," said Colleen Schwartz, director of communications for parent company Dow Jones.
The New York Times also reported on Tuesday that Cabello and other senior officials were under investigation by U.S. authorities as part of a wide-ranging inquiry into the cocaine trade. The charges could make it difficult for Venezuelan officials under investigation to travel or hold assets abroad, it said.
"These are grave accusations which suggest that our country has become a bridge for drug trafficking," said opposition leader Henrique Capriles, who narrowly lost a 2013 election to Maduro after Chavez's death from cancer.
Spanish newspaper ABC reported in January that a former member of Cabello's security detail had fled Venezuela and told U.S. authorities that he was involved in a drug ring.
Cabello, 52, a burly army lieutenant who joined Chavez's abortive 1992 coup attempt, filed a defamation lawsuit last month against 22 people linked to three media outlets for having republished information from that story.
He hinted on Tuesday that more lawsuits may follow.
"I've told those who reproduced the stories and all the stories that have come out: see you in the courts," he said.
"I won't give up, not today, not tomorrow."
Get Breaking news, live coverage, and Latest News from India and around the world on NDTV.com. Catch all the Live TV action on NDTV 24x7 and NDTV India. Like us on Facebook or follow us on Twitter and Instagram for latest news and live news updates.