Joaquín Guzman Lopez, 38, made his first court appearance at the Dirksen Federal Building.
He pleaded not guilty Tuesday in front of Judge Sharon Johnson Coleman.
Assistant U.S. Attorney Andrew Erskine went through the five drug and money laundering charges. For one of the charges, the maximum sentence is death.
Jeffrey Lichtman is representing Guzman Lopez, who is the son of Joaquin Guzman, commonly known as "El Chapo."
El Chapo was once the leader of the Sinaloa cartel and considered one of the most powerful drug traffickers in the world.
READ MORE: A son of El Chapo helped capture Sinaloa cartel leaders, officials say
El Chapo's son surrendered to U.S. authorities in El Paso, Texas last Thursday, which led to the arrest of Ismael Zambada, who goes by "El Mayo."
The 76-year-old El Mayo was allegedly left to oversee the cartel after El Chapo was convicted and sentenced to life in prison.
El Mayo allegedly co-founded the Sinaloa cartel with El Chapo, which has dominated drug sales in Chicago.
ABC7 Chicago legal analyst Gil Soffer called this a huge case for federal prosecutors.
"It's a very big case," Soffer said. "It's a big win for DOJ to be able to get the leaders of this cartel. They've been looking to get them for years and years, and what makes it all the more interesting is how he got here: the intrigue, the betrayal, the back-stabbing, the sons who turned against their fathers. You'd have to look long and far to find a story this complex and interesting, but this is a serious get for the DOJ."
Zambada and Guzman Lopez are accused of leading the cartel's criminal operations, including its deadly fentanyl manufacturing and trafficking networks.
Federal authorities say Guzman actually assisted with Zambada's capture.
Zambada was one of the Drug Enforcement Administration's most wanted fugitives.
The U.S. had been offering a $15 million reward to track him down.
Zambada entered a not guilty plea to all charges in El Paso on Friday.
Lichtman said Tuesday his client did not kidnap El Mayo, and has not made a deal with the government.
Guzman Lopez is next due in court Sept. 30.