MEXICO CITY—Dozens of Mexico’s most dangerous prisoners, cuffed hand and foot, boarded army jets under heavy guard this year, a rogue’s gallery of cartel leaders responsible for smuggling tons of heroin, fentanyl, cocaine and methamphetamine to insatiable U.S. buyers.

The men were rousted from prisons, where money and corruption provided them with weapons, cocaine, booze, women and phones to run their lucrative underworld empires from behind bars, coordinating drug shipments as well as ordering killings and kidnappings, U.S. and Mexican officials said.

The prisoners had no idea of their destination.

“Welcome to America!” said Derek Maltz, interim head of the Drug Enforcement Administration when he greeted the first batch of prisoners as they disembarked nine months ago. A second group arrived in August, a total of 55 men who face charges that could keep them locked in maximum-security prisons for the rest of their lives.

The prisoners represent the top echelons of Mexico’s biggest criminal organizations—the Sinaloa, Jalisco New Generation and Zetas cartels. They include Rafael Caro Quintero, who is charged with killing DEA agent Enrique “Kiki” Camarena in 1985 and has dodged extradition to the U.S. for decades. All are in custody without bail.

U.S. officials expect many of the prisoners will share firsthand knowledge about the operations of Mexico’s underworld—from smuggling secrets and money-laundering operations to the names of officials in government, the military, law-enforcement and finance who are paid to serve the drug-trafficking industry.

Cartel leaders in U.S. custody have for years had the opportunity to cooperate with authorities, sometimes in exchange for reduced sentences and more comfortable prison conditions.

Former Sinaloa cartel leader Joaquín “El Chapo” Guzmán, who has kept mum, spends 23 hours a day in a windowless U.S. prison cell, serving a life sentence. One of his sons, Joaquin Guzmán López, turned himself in to U.S. authorities last year and dragged along another wanted man, his godfather, Ismael “El Mayo” Zambada, the 70-something co-founder of the Sinaloa Cartel. Zambada, whose lawyer said was illegally brought to the U.S., has pleaded guilty to drug charges. He faces a life sentence at a Jan. 13 court hearing.

The younger Guzmán pleaded guilty in court Monday to drug-trafficking and money-laundering charges. He is cooperating with U.S. authorities, prosecutors said at the hearing.

Transferring 55 drug leaders to U.S. custody was a high-stakes undercover mission that drew 2,000 Mexican special forces. Officials feared that if word got out, kingpins would attempt escapes, set off riots or file legal appeals. Authorities also believed cartels might try to assassinate their own leaders, rather than risk them spilling secrets to U.S. law enforcement.

When the expulsion operation began, some prisoners thought they were headed to freedom, figuring their government bribes had paid off, a Mexican official said. Instead, they were shoved into armored personnel carriers and escorted to a military plane that flew them to the Altiplano maximum-security prison, about 50 miles west of Mexico City.

U.S. officials received word of the planned arrivals the night before the first operation. They made frantic calls to federal agents across the country: Many of the drug kingpins whom agents had spent years investigating would be landing the next morning.

The first prisoners boarded a half-dozen Mexican military planes on Feb. 27, headed to Chicago, Phoenix, San Antonio, New York and Dulles International Airport in Virginia. Rival drug lords who had ordered the killing of thousands of each other’s men sat side-by-side on the flight.

“Never in the history of our agency have we seen this level of bad guys being removed from Mexico,” Maltz, the former DEA chief, said in an interview.

Among them were the brothers Miguel Ángel and Omar Treviño, leaders of the paramilitary Zetas drug gang.

The setup

The Treviños have killed 18 prison officers since their capture more than 10 years ago, a senior Mexican official said, sometimes reciting the names out loud in a show of impunity. They controlled a network of more than 600 inmates in various locales, what officials called a prison cartel that terrorized communities from behind bars.

Officials monitored the brothers’ phone calls for clues that they had a hint of the removal plans. They worried the brothers’ private army of former Mexican special-forces soldiers would set fire to trailer-trucks and buses, blocking highways and stirring havoc in towns and cities if the Treviños learned what was in store.

An intelligence team spoke with rivals of the Treviños, men who revealed what they knew about the brothers’ informant networks and inner circle. They also gave information about the security teams that protected the brothers’ families.

Rivals provided the names of financial operators who paid informants, hit men and top-flight lawyers who might try to impede the brothers’ removal. The Treviños successfully thwarted extradition attempts 133 times through court appeals, according to the Mexican government.

Shackled and dressed in tan jumpsuits, the brothers descended the stairs of a Mexican military plane in Dulles, Va., escorted by Mexican special forces in balaclavas and black tactical gear and placed in the hands of U.S. authorities. They have since pleaded not guilty to drug trafficking and money-laundering charges.

Mexico expelled the 55 prisoners on national-security grounds, allowing Mexican officials to bypass requirements to notify the prisoners’ legal representatives. The removals were dubious from a legal standpoint, subverting due process and legal proceedings linked to extradition treaties signed by Mexico, say lawyers, security analysts and former officials.

The expulsion was taken “for the security and peace of our country, and is part of the collaboration with the U.S.,” President Claudia Sheinbaum said in September. The imprisoned cartel leaders threatened government officials, Mexican officials said. Lawyers representing several of the prisoners filed legal challenges afterward, but none succeeded.

Picking leaders from all major cartels and their factions showed that the Sheinbaum administration wasn’t favoring any of them, the officials said.

The idea of using Mexico’s national-security laws was first floated during the Biden administration, said people familiar with the bilateral talks. But the catalyst to action was pressure from the Trump administration, including the threat of punitive tariffs if Mexico didn’t step up its drug-trafficking enforcement, said one of the people familiar with the talks.

Mexican officials believe the expulsions have helped Sheinbaum avoid U.S. intervention. They feared that without stepped-up cooperation, the Trump administration might have conducted targeted killings or drone strikes on fentanyl labs, plunging U.S.-Mexico relations into a crisis.

Secretary of State Marco Rubio said last month at a Group of Seven summit in Canada that the U.S. wouldn’t conduct military operations in Mexico without consent from the Sheinbaum administration. “We’re not going to take unilateral decisions,” he said.

Convoy decoy

Weeks before the first man was escorted from his cell, authorities took control of more than a dozen Mexican prisons, hoping to avoid information leaks and escape attempts, officials said.

Prison directors were replaced. Catering companies were switched out to protect the men from poisoning. New camera-surveillance suppliers were hired. Prison custodians were replaced with special forces to avoid anyone tipping off cartel leaders. Some inmates were kept isolated to prevent information-sharing.

The military flights to the Altiplano prison required stopovers to pick up men from across Mexico. A wall of flat screens in a secret bunker in Mexico City kept track. A handpicked catering crew prepared meals under strict health-and-safety protocols. The prisoners got medical checkups to ensure they were delivered to the U.S. in good health, officials said.

The government consulted studies to identify the hours of lightest traffic from Altiplano to an airstrip near Mexico City, where the men would board flights to the U.S. Authorities set up facilities to house them for at least three days should flights to the U.S. be delayed, an official said.

Officials closely monitored Altiplano security-camera surveillance. The prison is where “El Chapo” staged a notorious escape in 2015, slipping through a hole in his cell into a tunnel equipped with a motorcycle on rails that led to a nearby safe house.

Servando “La Tuta” Gómez was one of the most closely watched. The former middle-school teacher ran methamphetamine labs in the state of Michoacán for years and collected enemies inside and outside of prison. As the day for his transfer to the U.S. drew closer, authorities monitored the communications of Gómez’s family, as well as bank activity by his closest confidants, watching for transactions that would suggest he was preparing an escape.

Mexico’s financial-intelligence unit froze bank accounts tied to shell companies that funded informant networks and used to pay their lawyers, according to another person familiar with the operation.

Days before Gómez’s transfer in August, special forces left the prison in a convoy of armored vehicles headed to Mexico City as a decoy, passing through areas where Gómez commanded loyal underlings. A second, more discreet convoy ferried the drug lord on a different route, the person said. A drone flew above the convoys providing surveillance.

Gómez faces drug-trafficking charges in the U.S. and has a court hearing scheduled this month. His lawyer declined to comment.

A third transfer of Mexican drug bosses to the U.S. is under discussion, said people familiar with the plans.

Write to Santiago Pérez at santiago.perez@wsj.com