The vast Brooklyn, New York, courtroom fell silent as the verdict was read. Jurors did not look at the defendant, who pocketed nearly $14 billion as the decadeslong head of the murderous Sinaloa cartel.
There was no visible reaction from Guzmán, whose conviction on the top charge of engaging in a continuing criminal enterprise carries a mandatory term of life in prison. He will be sentenced on June 25.
"It is a sentence of which there is no escape and no return, " US Attorney for the Eastern District Richard Donoghue said.
US District Judge Brian Cogan confirmed the verdicts with each of the eight women and four men on the jury, telling them later their conduct on the panel "made me very proud to be an American."
One of Guzmán's lawyers described him as "extremely upbeat" after the verdict.
"He's a fighter," defense attorney Michael Lambert said. "He's not done yet by far."
After jurors left the room, Guzmán waved and smiled at his wife, Emma Coronel, a former beauty queen and courtroom regular who smiled back and touched her hand to her heart.
"Good, thank you," she said in Spanish when asked how she felt after the verdict.
The partially sequestered and anonymous jury deliberated roughly 34 hours over six days.
Over 2½ months, they sat through testimony about unspeakable torture and ghastly murders, epic corruption at nearly every level of Mexico's government, narco-mistresses and naked subterranean escapes, gold-plated AK-47s and monogrammed, diamond-encrusted pistols.
"We are obviously disappointed with the jury's verdict in the trial of Joaquín Guzmán Loera but are respectful of the process and the jury's decision," defense attorney Eduardo Balarezo said. "We were faced with extraordinary and unprecedented obstacles in defending Joaquín. ..."
Another member of the defense team, Jeffrey Lichtman, said they waged a vigorous defense against an "avalanche" of evidence and cooperating witnesses. They plan to file an appeal on a number of issues.
"He was bringing our spirits up, which was surprising. Usually it's the other way around," Lichtman said of his client after the verdict. "He's always been a gentleman, always been supportive, always been happy and appreciative of all our efforts."
Donoghue said the case represented a victory for the American people, for Mexicans who had lost loved ones in drug wars, and for every family who has lost someone to drug addiction.
"There are those who say the war on drugs is not worth fighting. Those people are wrong," he said.
The case, Donoghue said, pulled back the curtain on international drug trafficking in a way no trial ever has, revealing the endemic corruption that allowed the Sinaloa cartel to operate.
"This is a day of reckoning, but there are more days of reckoning to come," he said.
Guzmán, 61, was convicted of 10 counts, including engaging in a continuing criminal enterprise, conspiracy to launder narcotics proceeds, international distribution of cocaine, heroin, marijuana and other drugs, and use of firearms.
He faces a mandatory life sentence without the possibility of parole for leading a continuing criminal enterprise, and a sentence of up to life imprisonment on the remaining drug counts.
Federal prosecutors said they will seek a forfeiture judgment for billions of dollars constituting the cartel's illegal drug-trafficking proceeds.
The prosecution's case featured 200 hours of testimony from 56 witnesses. Fourteen of those witnesses -- mostly admitted drug traffickers and cartel associates -- cooperated with prosecutors in hopes of reducing their own prison sentences.
There were also surveillance photos, intercepted phone calls and text messages involving Guzmán, as well as exhibits of blingy firepower and bricks of cocaine that dropped with the force of potato sacks.
Guzmán, once listed on Forbes' Billionaires List, has long been a slippery and near-mythical figure. He escaped from a Mexican prison in 2001 in a laundry cart and again in 2015 through a tunnel. After he was recaptured in 2016, he was extradited to the US to face American federal charges.
The high-profile trial centered on the struggles and actions of El Chapo, who came from humble origins in the heart of Mexico's rugged three-state Golden Triangle to become its most infamous native son.
The 12-week proceedings were conducted in part during the partial government shutdown over funding for a border wall. It showed that such fortification would have failed to stop tons of drugs the cartel moved from Mexico to the United States via fishing boats, trains, tractor-trailers, radar-evading airplanes, passenger cars at legal ports of entry, submarines, oil tankers, cocaine-laden cans of jalapeños and cross-border tunnels.
It included stunning testimony of corruption at nearly every echelon of Mexico's government, from police and military commanders to local and state officials to former presidents who vehemently denied the allegations.
The courtroom drama drew celebrities and so-called narco-tourists attracted to the Latin American soap opera atmosphere of the proceedings. Guzmán appeared in a suit and tie each morning, delivering a wave and smile to Coronel in the second row.
Under El Chapo, the Sinaloa cartel smuggled narcotics to wholesale distributors in Arizona, Atlanta, Chicago, Los Angeles, Miami, New York.
About noon Tuesday, the court learned there was a verdict.
Some court-watchers had suggested the longer jurors considered the case, the better the chances they would acquit Guzmán or hang on any of the 10 counts. Others said jurors seemed simply to be doing their due diligence, sifting through hundreds of hours of testimony.
Still, Guzmán's plainclothes visits to the courthouse and his interactions, however minimal, with his allies had lightened his mood these last months, defense attorney Michael Lambert said. It was in sharp contrast with solitary confinement, with little to no human interaction for as many as 23 hours a day.
"Once the trial started, he seemed a little happier, a little more engaged," he said. "Just sitting there in a suit without handcuffs on is a privilege in itself. It makes him feel human."
CNN's Maria Santana and Eric Levenson contributed to this report.