The long-awaited trial of Guzman, who prosecutors believe hired assassins to knock off rivals with a string of accused violent acts to protect the cartel, will start with the jury pool arriving answering a lengthy questionnaire, according to the New York Post.
The former leader of the Sinaloa Cartel was extradited to the United States from Mexico early last year.
Federal prosecutors say from January 1989 to December 2014, Guzman's cartel was responsible for importing and distributing massive amounts of illegal narcotics and killed those who threatened the enterprise.
"El Chapo" is also charged with using firearms in running a drug trafficking and money laundering operations, while making $14 billion in cash from the sale of narcotics throughout the United States and Canada.
Guzman is known for a series of daring prison escapes, including a 2015 escape from Mexico's most secure prison via a tunnel under his cell's shower. He has been under tight security as he awaits trial.
Jurors selected for the trial will be escorted by federal guards to and from the courthouse, officials said.
In another security move, the names of trial witnesses were blacked out on court documents as prosecutors feared that their cooperation would make them targets for the cartel. Some have even been hiding in special jail units and others in witness protection programs, WNBC-TV reported.