The Justice Department called Maduro the head of a cocaine trafficking group called "The Cartel of the Suns" that exported hundreds of tonnes of drugs working hand in hand with the Revolutionary Armed Forces of Colombia, which the United States has officially labelled a "terrorist organization."
Also indicted were more than a dozen other officials of the Maduro regime, including members of the Venezuelan military and judiciary, including the country's chief justice.
The indictments were issued in multiple US jurisdictions including New York and Miami, with charges running from "conspiracy to narco-terrorism" to money laundering.
"For more than 20 years, Maduro and a number of high-ranking colleagues allegedly conspired with the FARC, causing tons of cocaine to enter and devastate American communities," said Attorney General Bill Barr.
"It's time to call out this regime for what it is," he said.
"The Maduro regime is awash in corruption and criminality."
Barr said the Maduro regime had supported a breakaway group of the FARC along the Colombian-Venezuelan border that is involved in drug trafficking.
Also being charged are Diosdado Cabello, the Venezuelan National Assembly's former speaker, Defense Minister Vladimir Padrino Lopez, former military intelligence head Hugo Armando Carvajal Barrios, former general Cliver Antonio Alcala Cordones, and Chief Justice Maikel Moreno.
The State Department also announced a $10 million rewards for Cabello, Alcala and Carvajal.