Guzmán, 61, faces 10 counts, including engaging in a continuing criminal enterprise, conspiracy to launder narcotics proceeds, global distribution of cocaine, heroin, marijuana and other drugs, and use of firearms.
They were are asked to make 53 decisions about whether prosecutors have proven various elements of the 10-count indictment against Mexican drug kingpin Joaquin "El Chapo" Guzman.
The trial testimony lasted almost three months and the jurors have been tasked with deciding on 10 separate counts.
El Chapo is now facing life in maximum security prison after a jury consisting of five men and seven women revealed the verdict to the three-month-long trial.
Guzman faced a drumbeat of drug-trafficking and conspiracy convictions that could put the 61-year-old escape artist behind bars for decades in a maximum-security USA prison selected to thwart another one of the breakouts that embarrassed his native country.
In the trial, which has lasted several months, prosecutors used more than 50 witnesses to detail Guzman's involvement in making billions of dollars distributing drugs in the U.S.
As the judge read the verdict, Guzman stared at the jury, and his wife watched the scene, both with resignation in their faces. Guzman's lawyers did not deny his crimes as much as argue he was a fall guy for government witnesses who were more evil than he was.
The drug lord, 61, faced charges of running a large-scale drug operation as the head of the Sinaloa drug cartel.
In contrast, defense attorneys called just one witness and focused on undermining the credibility of cooperating witnesses.
Jurors in federal court in Brooklyn convicted Guzman, 61, head of the Sinaloa Cartel, on all 10 counts brought by United States prosecutors.
Defence attorney Jeffrey Lichtman urged the jury in closing arguments not to believe government witnesses who "lie, steal, cheat, deal drugs and kill people".
Guzman spoke in the courtroom only once during the trial, saying he would not testify in his own defense, NBC News reported.
Chapo was detained by the Mexican government in 2014 but escaped a year later.
Guzman, whose nickname means "Shorty", was extradited to the United States for trial in 2017 after he was arrested in Mexico the year before. She said Guzman led her to a trap door beneath a bathtub that opened up to a tunnel that allowed them to escape. "He left us behind".
He was recaptured several months later - his third arrest in 23 years - in the Sinaloa coastal city of Los Mochis and extradited to the USA about a year later. Perhaps most famously, he escaped a Mexican prison in 2015 through an elaborate tunnel that included an adapted motorcycle on rails.