U.S. prosecutors say that as the head of the Sinaloa Cartel since 2003, Guzman directed the movement of multi-ton shipments of drugs including heroin, cocaine, marijuana, and methamphetamine across borders and into the United States.
These ordinary men and women will determine whether Guzman - the diminutive father of two whose nickname means "shorty" - is guilty or not of 11 trafficking, firearms and money laundering charges.
El Chapo made world headlines in July 2015 when he slipped out of his cell at the maximum security Altiplano federal prison via a mile-long underground tunnel.
Guzman, 61, formerly led the Sinaloa Cartel, named after its base in the Mexican state of Sinaloa, which became one of the most powerful drug trafficking organizations in the world.
"Guzman Loera is accused of using violence, including torture and murder, to maintain an iron-fisted grip on the drug trade across the U.S. -Mexico border, ' then-Brooklyn U.S. Attorney Robert Capers said".
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.
One of Mexico's most notorious drug lords will go on trial in the United States later on Monday.More news: Raptors' Kawhi Leonard sits vs. Lakers with foot soreness
Guzman is pleading not guilty but the government has presented a wealth of evidence that includes more than 300,000 pages and at least 117,000 audio recordings.
"It's probably set up to be the most expensive trial in the history of the United States", he said. Even Guzman's lawyers are in the dark as to all the former associates, hired hands or rivals who have turned informants.
Some of the informants have already been absorbed into the USA witness protection programme and given new identities and homes around the country.
And for further protection- the jurors names will be withheld from the public.
He has been in solitary confinement in a high-security NY prison since Mexico extradited him to the United States in January 2017.
He was arrested again by Mexican marines in February 2014 but escaped 14 months later before being re-captured in January 2016. Gómez said a journey to the rugged Sierra Madre by American actor Sean Penn put investigators on Guzman's doorstep.